Embodiments disclosed herein provide compositions for increasing CCL3 and/or CCL4 interactions with CCR5 and/or CCR1 to enhance an immune response. Applicants identified specific interactions between CD8+ T cells and inflammatory monocytes/macrophages that change during tumor progression from small to medium to large tumors. The ligands CCL3 and CCL4 are expressed in a specific subset of T cells (CD8+ PD-1+ TIM3+ T cells). The receptors CCR5 and CCR1 are expressed in inflammatory monocytes/macrophages. Modulation or maintenance of these interactions can allow enhanced immune responses for treating cancer, as well as for vaccination.
Chimeric small molecules comprising an immunogenic display moiety and methods of using the chimeric small molecules to label proteins with the immunogenic display moiety for MHC display on the surface of a cell or to label cell surface proteins with the immunogenic display moiety for display on the surface of a cell, thereby inducing an immune response.
C07K 16/42 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against immunoglobulins (anti-idiotypic antibodies)
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
Systems, methods and composition for targeting polynucleotides are detailed herein. In particular, engineered DNA-targeting systems comprising novel TnpB polypeptides and a reprogrammable targeting nucleic acid component and methods and application of use are provided.
Systems, methods and composition for targeting polynucleotides are detailed herein. In particular, engineered DNA-targeting systems comprising novel TnpB polypeptides and a reprogrammable targeting nucleic acid component and methods and application of use are provided.
The present disclosure provides compounds of Formulae T-A, I-B. II-A. II-B. lll-A, III-B, IV-A. IV-B, V-A, V-B, Vl-A, and VI-B. and compounds shown in Table 13, Table 13 A, and Table 14, and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled compounds, and prodrugs thereof, which are GSK3 inhibitors. The present disclosure also provides pharmaceutical compositions, combination therapies, and kits comprising the compounds, and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crysials, tautomers, stereoisomers, isotopically labeled compounds, or prodrags thereof, and methods of treating or preventing diseases and disorders associated with GSK3.
A61K 31/4745 - Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
The present invention provides novel cyclic nucleotide derivatives and analogs based on the discovery of novel second messengers generated in human cells in response to challenges to the innate immune system. Compositions find use in modulation of innate immune signaling.
C07H 21/02 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
A61K 31/712 - Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
A61K 31/7125 - Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
11212 2 are each a linker; and E is an electrophilic reactive group. Molecules according to the present invention find use making substrate modifications such as post-translational modifications to targets that are not the natural substrate of the kinase; accordingly, diseases or disorders may be treated or prevented with molecules of the present disclosure.
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
HTTFXNFXN genes. Complexes, compositions, and systems comprising a prime editor and any of the pegRNAs disclosed herein are also provided by the present disclosure. The present disclosure further provides polynucleotides, vectors, AAVs, cells, compositions, and kits. Methods of treating Huntington' s disease and Friedreich's ataxia, as well as uses of the compositions, pegRNAs, and systems described herein, are also provided herein.
The present disclosure provides compositions and methods useful in the treatment of trinucleotide repeat disorders, including Huntington's disease and Friedreich's ataxia. The present disclosure also provides gRNAs designed to target the HTT or FXN genes. Complexes comprising a base editor and any of the gRNAs disclosed herein are also provided by the present disclosure. The present disclosure further provides polynucleotides, vectors, cells, compositions, and kits. Methods of treating Huntington's disease and Friedreich's ataxia are also provided herein.
The present invention discloses methods and platforms for generating protein binding proteins with specificity for native peptide-MHC (pMHC) complexes. The pMHC binding proteins can be used in bi-specific antibodies or for generating CAR T cells capable of binding to peptides bound to specific MHC alleles.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
11.
ARTIFICIAL INTELLIGENCE ENABLED DISCRIMINATION OF DISEASE AND DISEASE ETIOLOGY
The subject matter disclosed herein relates using waveform data of a subject to detect one or more diseases or disease etiologies. Particular examples relate to providing a system, a computer-implemented method, and a computer program product to waveform data to detect and differentiate particular diseases and disease etiologies with machine learning models.
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
G16H 50/70 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for mining of medical data, e.g. analysing previous cases of other patients
Described in certain example embodiments herein are programmable nuclease¬ peptidase compositions, systems, and methods for the manipulation of nucleic acids and/or polypeptides. In some embodiments, the programmable nuclease-peptidase composition comprises a repeat-associated mysterious protein (RAMP) polypeptide; a guide molecule capable of forming a RAMP-guide molecule complex with the RAMP polypeptide and directing sequence specific binding of the complex to a target polynucleotide; and a peptidase capable of binding to the RAMP polypeptide, the guide molecule, or further complexing with the RAMP-guide molecule complex, wherein binding of the RAMP-guide molecule complex to the target polynucleotide initiates binding and/or interaction of the peptidase with a target polypeptide.
13.
METHODS FOR TREATMENT SELECTION FOR CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)
As described below, the present invention features compositions, panels of biomarkers, and methods for selecting a subject with chronic lymphocytic leukemia (CLL) for treatment using an agent and/or for inclusion in a clinical trial using the agent to treat CLL.
Aspects of the disclosure relate to Botulinum toxin X (BoNT X) protein variants. The variants provided herein have been evolved to cleave GTP cyclohydrolase 1 (GCH1). Some of the variants provided herein were evolved from a procaspase- 1 cleaving polypeptide. Further aspects of the disclosure relate to nucleic acids encoding the GCH1 cleaving polypeptides described herein and expression vectors comprising the nucleic acids, as well as host cells and fusion proteins comprising the GCH1 cleaving polypeptides described herein, and kits comprising the GCH1 polypeptides, fusion proteins, nucleic acids, expression vectors, or host cells described herein. Further aspects of the disclosure relate to methods of producing BoNT X variants and methods of using the BoNT X protein variants, for example, to reduce pain.
T-type voltage-gated calcium channel potentiators are described herein which are able to augment thalamic function, for example, decrease thalamocortical hyperactivity in patients in need thereof. These potentiators may be useful in many diseases or conditions associated therewith such as schizophrenia and neurodevelopmental disorders. The Cav potentiators typically have the structure of Formula (I) or Formula (V).
A61K 31/166 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon atom of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
A61K 31/407 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
The present disclosure provides a protein which is composed of a sequence including one amino acid sequence among the following (a)-(c) and forms a complex with a guide RNA: (a) an amino acid sequence which includes an amino acid sequence composed of at least amino acid numbers 198-614 in the amino acid sequence represented by SEQ ID NO: 1, and includes a substitution of one or both of E172 and E297; (b) an amino acid sequence in which at least one amino acid is deleted, inserted, substituted, or added in portions other than amino acid numbers 172 and 297 in the amino acid sequence represented by (a); and (c) an amino acid sequence which shares an identity of at least 80% with portions other than amino acid numbers 172 and 297 in the amino acid sequence represented by (a). This protein is a Cas13bt3 variant having improved efficiency and specificity.
The present invention relates to systems, compositions, and methods for altering nucleic acids, such as at a single position (e.g., A/T to G/C or G/C to A/T; in a gene with disease causing SNP). In particular, the present invention relates to engineered CRISPR/Cas systems comprising: a first Cas protein (e.g., Cas5-8 or Cas11) which is optionally tethered or fused to an effector protein selected from: i) an adenine deaminase, ii) a uracil glycosylase inhibitor, or iii) an APOBEC protein; and at least one guide RNA (gRNA) configured to hybridize to a portion of a target nucleic acid sequence. In certain embodiments, the systems further comprise a second Cas protein selected from: i) Cas3, ii) a helicase-deficient Cas3; or iii) a single-strand nicking Cas endonucleases (e.g., Cas9 Nickase H840A Protein).
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
20.
EVOLVED CYTOSINE DEAMINASES AND METHODS OF EDITING DNA USING SAME
The present disclosure generally relates to evolved cytidine deaminases derived from cytidine deaminases, and methods of editing DNA using the same. In some aspects, the disclosure describes the directed evolution of a TadA-derived adenosine deaminase (TadA- CD) to perform cytidine deamination. In some embodiments, the TadA-CDs comprise a plurality of mutations compared to the parent TadA variant. In some embodiments, the TadA-CD is fused to a programmable DNA binding protein. Other aspects of the disclosure generally relate to a cytosine base editor (CBE) comprising a programmable DNA binding protein and the TadA-CD. In some embodiments, the disclosed cytosine base editor has improved efficiencies of conversion and reduced off-target editing frequencies compared to naturally-occurring CBEs. Also provided are polynucleotides, vectors, and kits useful for the generation and delivery of the CBEs. Cells containing such vectors and CBEs are also provided. Further provided are methods of treatment comprising administering the CBEs.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
C12N 9/78 - Hydrolases (3.) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
21.
METHODS AND COMPOSITIONS FOR TRANSDUCING HEMATOPOIETIC CELLS
Described herein are hematopoietic cell-specific targeting moieties and compositions including the hematopoietic cell specific targeting motifs. Also described herein are uses of the hematopoietic cell-specific targeting motifs and compositions including the hematopoietic cell specific targeting moieties. In some embodiments, the hematopoietic cell-specific targeting moieties and compositions including the hematopoietic cell specific targeting moieties can be used to direct delivery of a cargo to a hematopoietic cell.
A61K 47/00 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
The present invention relates to 1H-pyrrolo[3,2-b]pyridine derivatives of formula (I) as irreversible inhibitors of mutant EGFR for the treatment of cancer. An exemplary compound is e.g. N-[2-({4-[3-(4-fluorophenyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-3-yl}oxy)ethyl]prop-2-enamide (example 1). Pharmacological data of exemplary compounds is provided (AA).
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
Described in several example embodiments herein are engineered programmable pattern recognition compositions and uses thereof. In certain example embodiments, the engineered protein contains an NTPase of a Signal Transduction ATPases with Numerous- associated Domains (STAND) superfamily (STAND NTPase), comprising a pathogen- associated molecular pattern (PAMP) recognition activity, wherein the STAND NTPase and the PAMP recognition activity are derived from the same or different prokaryotes.
T cell responses are exquisitely antigen-specific and directed against peptide epitopes displayed by human leukocyte antigen (HLA) on the surface of presenting cells. In particular, class II HLA (HLA-II) is remarkably polymorphic, which allows for presentation of diverse peptide antigens to T cells, but also forms the basis for genetic associations with diverse immunopathologies across the spectrum of infectious disease and autoimmunity. Here, Applicants employ monoallelic immunopeptidomics to retrieve over 200,000 unique peptides presented by 41 HLA-II heterodimers covering major alleles across diverse ancestries. Applicants leveraged this expansive dataset to develop computational models that predict peptide antigens based on HLA-II binding properties and infer informative features of the protein antigens from which these peptides derive. Combining both peptide and (contextual) protein features, Applicants develop Context Aware Predictor of T cell Antigens (CAPTAn) to discover novel T cell epitopes from prokaryotes in the human microbiome and the viral pandemic pathogen SARS-CoV-2.
Engineered or non-naturally occurring systems and compositions comprising novel Cas5- HNH and Cas8-HNH polypeptides are detailed herein. Also provided are methods and applications for the novel Cas5-HNH and Cas8-HNH polypeptides for reprogrammable targeting nucleic acid and polynucleotide components.
C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
C12N 15/63 - Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
C12N 15/62 - DNA sequences coding for fusion proteins
C12N 15/66 - General methods for inserting a gene into a vector to form a recombinant vector using cleavage and ligation; Use of non-functional linkers or adaptors, e.g. linkers containing the sequence for a restriction endonuclease
27.
AAV CAPSIDS THAT ENABLE CNS-WIDE GENE DELIVERY THROUGH INTERACTIONS WITH THE TRANSFERRIN RECEPTOR
An engineered AAV capsid is provided, in which at least one protein on the capsid is modified to include a n-mer motif, which promotes transduction of the capsid into the central nervous system (CNS) through interaction with the Transferrin receptor. Further embodiments provide a vector system comprising one or more vectors encoding AAV capsids and a method of delivering cargo to the CNS. The method comprises administering, in vivo or in vitro, a AAV capsid according to embodiments described herein and the AVV capsid comprises one or more cargo molecules.
The subject matter disclosed herein is generally directed to treating cancers sensitive to phosphate dysregulation with inhibitors of inositol pyrophosphate (PP-InsP) synthesis, in particular, inhibitors of inositol hexakisphosphate kinases IP6Ks.
Described in certain example embodiments herein are engineered delivery vesicle generations systems capable of producing engineered delivery vesicles containing two or more different retroelement polypeptides. Also described herein are methods of making and using the engineered delivery vesicles, such as to deliver one or more cargoes.
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
C12N 15/11 - DNA or RNA fragments; Modified forms thereof
30.
COMPOSITIONS AND METHODS FOR PREPARING CAPPED CIRCULAR RNA MOLECULES
The present disclosure provides compositions, reagents, and methods for producing capped, circular RNA molecules, circularized RNA molecules, and in particular, circularized mRNA molecules encoding a polypeptide such as a therapeutic protein.
Aspects of the disclosure relate to compositions and methods for targeted protein degradation. In some embodiments, the disclosure relates to methods of evolving protein degrons to interact with certain small molecule inducers (e.g., VS-777, PT- 179, or PK-1016). In some embodiments, the disclosure relates to compositions (e.g., peptides, nucleic acids encoding the protein degrons, etc.) used for targeted protein degradation. In some embodiments, the disclosure relates to methods of degrading a target polypeptide in a cell.
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
Provided herein arc compounds of Formula (I- A), (I-B), or (I-C), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically enriched forms, prodrugs, or mixtures thereof, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing diseases and/or conditions (e.g., neurological disease (e.g., Alzheimer's disease, multiple sclerosis, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis), metabolic disorder (e.g., obesity, diabetes, X-linked adrenoleukodystrophy (X-ALD)), proliferative disease (e.g., cancers), hepatic disease (e.g., liver cirrhosis), conditions associated with autophagy (e.g., neurodegenerative disease, infection, cancer, conditions associated with aging, heart disease), conditions associated with aging, conditions associated with modulating the mPTP, cardiovascular conditions (e.g., ischemia-reperfusion injury), stroke, heart attack, conditions associated with oxidative stress, mitochondrial diseases, or other diseases associated with cyclophilins) in a subject, as well as for reducing oxidative stress. Provided are methods of inhibiting a cyclophilin in a subject, cell, tissue, and/or biological sample. Provided are methods of selectively inhibiting a cyclophilin (e.g., CypD, CypE) in a subject, cell, tissue, and/or biological sample.
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
C07K 7/56 - Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring the cyclisation not occurring through 2,4-diamino-butanoic acid
The present disclosure provides Cas protein variants comprising one or more amino acid substitutions relative to wild-type Casl4al. Fusion proteins comprising the Cas protein variants described herein are also provided by the present disclosure. Further provided herein are methods for modifying a target nucleic acid using the Cas proteins and fusion proteins provided herein. The present disclosure also provides guide RNAs, complexes, polynucleotides, systems, cells, kits, and pharmaceutical compositions.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
C12N 15/63 - Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
Described and featured are compositions, a system and methods for identifying and selecting substrates of E3 ligases by ubiquitin biotinylation. The components of the compositions, system and methods are ubiquitin- and interaction-specific, thereby providing the enrichment and identification of endogenous or exogenous E3 ligase substrate molecules that are proximally ubiquitinated and biotinylated by components designed to interact both physically and functionally in the compositions, system and methods. The compositions, system and methods are useful and advantageous for identifying and selecting E3 ligase substrates (and/or associated molecules) that are modulated or induced by other agents, such as immunomodulatory imide agents (IMiDs), molecular glues and bifunctional proteolysis targeting chimeras (PROTAC®s).
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
C12N 9/00 - Enzymes, e.g. ligases (6.); Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating, or purifying enzymes
C12N 15/62 - DNA sequences coding for fusion proteins
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
The disclosure features compositions, systems, and methods for preparation and use of efficient RNA nuclear export of ribozyme-assisted circular RNA molecules (racRNAs). In embodiments, the methods involve characterizing a cell or tissue using racRNAs.
C12N 15/11 - DNA or RNA fragments; Modified forms thereof
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
Chimeric, engineered DNA-targeting IscB systems, methods and compositions including novel chimeric IscB polypeptides and reprogrammable targeting nucleic acid components and methods and application of use are provided.
The present disclosure provides zinc finger domain-containing proteins comprising optimized a-, P-, and linker motifs, and fusion proteins comprising said zinc finger domain-containing proteins fused to an effector domain. The present disclosure also provides double-stranded DNA deaminase A (DddA) variants and fusion proteins comprising said DddA variants fused to a programmable DNA binding protein (e.g., any of the zinc finger domain-containing proteins disclosed herein, a TALE protein, or a CRISPR/Cas9 protein). Methods for editing DNA (including genomic DNA and mitochondrial DNA) using the fusion proteins described herein are also provided by the present disclosure. The present disclosure further provides polynucleotides, vectors, cells, kits, and pharmaceutical compositions comprising the zinc finger domain-containing proteins, DddA variants, and fusion proteins described herein.
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
39.
ENGINEERED VIRAL VECTORS WITH ENHANCED PACKAGING CAPACITY AND METHODS OF USING THE SAME
Provided are engineered viral vectors, compositions comprising viral vectors, and methods of producing and using engineered viral vectors. The engineered viral vectors provided herein include capsid proteins derived from densovirus (DNV). Such DNV capsid proteins can assemble in mammalian cells and encapsulate adeno-associated virus (AAV) and/or DNV genomic DNA. The engineered viral vectors may be used as delivery vectors in target gene therapies.
C12N 7/00 - Viruses, e.g. bacteriophages; Compositions thereof; Preparation or purification thereof
C12P 19/34 - Polynucleotides, e.g. nucleic acids, oligoribonucleotides
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
C12N 15/11 - DNA or RNA fragments; Modified forms thereof
40.
ENGINEERED PNMA PROTEINS AND DELIVERY SYSTEMS THEREOF
Described herein are engineered paraneoplastic Ma protein (PNMA) capable of forming a capsid. In some embodiments, the engineered PNMA proteins comprise one or more modifications that enhance binding or loading of a cargo into the capsid, one or more modifications that modify cell-specificity of the capsid, one or more modifications that enhance intracellular delivery of the capsid, or a combination thereof. Also described herein are delivery systems comprising capsids comprising an engineered PNMA protein and a cargo.
Engineered capsid scaffolds comprising one or more modified capsid proteins are described exhibiting properties of improved thermostability while producing at similar levels to the naturally occurring capsid serotype. Embodiments include use and delivery of the engineered capsid scaffolds to allow for increased tolerance for manipulation and mutagenesis.
This invention provides compositions, reagents, methods, and kits for producing derivatized RNA molecules, particular mRNA molecules encoding a polypeptide and in particular a therapeutic protein, derivatized by linkage to a peptide, aptamer, synthetic DNA or RNA oligonucleotide or molecular probe, capable of targeting the derivatized RNA molecules to a particular subcellular location in a target cell.
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
The disclosure features compositions containing chimeric antigen receptor (CAR) immune cells that have been modified to reduce and/or eliminate expression or activity of a natural killer cell lectin A (NKG2A) polypeptide and/or a cluster of differentiation 94 (CD94) polypeptide, and methods for use thereof to treat a neoplasia.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
Described in certain example embodiments herein are programmable nuclease¬ peptidase compositions, systems, and methods for the manipulation of nucleic acids and/or polypeptides. In some embodiments, the programmable nuclease-peptidase composition comprises a repeat-associated mysterious protein (RAMP) polypeptide; a guide molecule capable of forming a RAMP-guide molecule complex with the RAMP polypeptide and directing sequence specific binding of the complex to a target polynucleotide; and a peptidase capable of binding to the RAMP polypeptide, the guide molecule, or further complexing with the RAMP-guide molecule complex, wherein binding of the RAMP-guide molecule complex to the target polynucleotide initiates binding and/or interaction of the peptidase with a target polypeptide.
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
Nucleic acid molecules, compositions, recombinant AAV (rAAV) particles, kits, and methods are described herein for delivering a base editor (or "nucleobase editor") to cells, e.g., via AAV vectors. In particular, the disclosure provides compositions, methods, and uses for delivery of adenine base editors and cytosine base editors in a single AAV vector (or genome). Further described herein are improved AAV vectors containing size-minimized regulatory components that enable, e.g., the packaging of base editors. Provided herein are methods and compositions for delivering base editor proteins to a cell or tissue in a single recombinant AAV (rAAV) vector. Contemplated herein are improved methods and compositions for delivering these base editors in vivo, in a single rAAV particle. Further provided herein are base editors and compositions and cells comprising these base editors.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
Disclosed herein are various improvements in prime editing (PE) relating to the optimization of various aspects and parameters of PE, including optimizing the conducting of PE and twin prime editing ("twinPE") experiments, as well as optimizing the design of pegRNAs and second-strand nicking guide RNAs.
Provided are isolated enhancer element sequences that regulate and restrict expression of a transgene, such as a therapeutic gene, to certain neuronal cell types and/or populations in the brain and CNS. Therapeutic virus vectors containing the cloned enhancer element sequences, particularly, recombinant adeno-associated virus (rAAV) vectors, and a transgene are described. The rAAV vectors, compositions and methods are useful for treating subjects afflicted with neuropsychiatric and neuropathological diseases, disorders and conditions and symptoms thereof. The vectors can be used to restore normal cellular function, e.g., by restoring expression of certain genes to the appropriate interneuron or neuron target cell populations, to address the root cause of the disease, e.g., by restoring the excitation-inhibition balance in the neuronal cell or cell population.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
C12N 15/63 - Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
Described in various embodiments herein are tiled amplification nucleic acid detection systems and uses thereof. In some embodiments, the nucleic acids amplified and detected are cell free DNA (cfDNA).
The present disclosure provides Cas9 variants, and base editors comprising these variants, that recognize non-canonical protospacer adjacent motifs (PAMs) and have less restrictive PAM requirements for editing. The present disclosure provides Cas9 protein variants comprising one or more amino acid substitutions relative to wild-type Nme2Cas9. Fusion proteins comprising the Cas protein variants described herein are also provided by the present disclosure. Further provided herein are methods for editing a target nucleic acid using the Cas variants and fusion proteins provided herein. The present disclosure also provides guide RNAs, complexes, polynucleotides, cells, kits, and pharmaceutical compositions. Further described herein are phage-assisted continuous evolution (PACE) systems, vectors, methods, and devices.
112122 are each a linker; and E is an electrophilic reactive group. Molecules according to the present invention find use making substrate modifications such as post-translational modifications to targets that are not the natural substrate of the kinase; accordingly, diseases or disorders may be treated or prevented with molecules of the present disclosure.
Engineered ionophores capable of increased metal ion transport across hydrophobic membranes and/or reduced metal ion binding affinity, pharmaceutical compositions thereof, kits thereof, ion-selective membrane devices thereof, and methods of use thereof. Hydrophobic membranes can be biological, e.g., cell membranes, or nonbiological, e.g., ion-selective membranes. Engineered ionophores can comprise a metal ion chelator group comprising: a polar binding site having binding atoms to form a metal ion chelate complex; and one or more shielding group(s) in proximity to the binding atoms. Shielding groups can increase the hydrophobic membrane permeability and reduce the binding affinity of the chelate complex. Methods of use can comprise contacting said membranes with said engineered ionophores, metal ion chelate complexes thereof, pharmaceutical compositions thereof, the components of kits thereof, or the like, or any combination thereof. Methods of treatment comprise administering the same to a human or non-human animal, plant, or part thereof, e.g. cells.
B01D 69/02 - Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor characterised by their properties
The present disclosure relates to treating mitochondrial diseases, cancer and other conditions as a result of reduced oxidative phosphorylation (OXPHOS) activity by overexpressing the METTL17 gene, encoding methyltransferase-like 17. Currently, overexpression of METTL17 to increase its copy number and/or intra-mitochondrial activity has not been indicated as a possible therapeutic for treating mitochondrial disease or other diseases such as cancer or aging related to a decline in OXPHOS activity. A variety of gene therapy approaches are presented for overexpression of METTL17 including, but not limited to, AAV, adenovirus and lentiviral vector expression.
Microscaled proteogenomics was deployed to probe the molecular basis for differential response to neoadjuvant carboplatin & taxotere combination chemotherapy for triple-negative breast cancer (TNBC). Proteogenomic analyses of somatic copy number aberrations identified a resistance-associated 19q13.31-33 deletion where LIG1, POLD1 and XRCC1 are located, in orthogonal datasets, LIG1 (DNA ligase I involved in lagging strand synthesis) gene deletion and/or low mRNA expression were associated with lack of pathological complete response and poor prognosis in TNBC, as well as selective carboplatin-resistance in TNBC patient-derived xenograft models. Low expression or LIG1 loss was also associated with higher chromosomal instability index (CIN) and poor prognosis in other cancer types, demonstrating that deletion of lagging- strand synthesis components has broad clinical significance.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
57.
SMALL NOVEL CRISPR-CAS SYSTEMS AND METHODS OF USE THEREOF
Engineered or non-naturally occurring systems and compositions comprising novel Type V Cas polypeptides and orthologs thereof are disclosed herein. Also provided are methods of use for the novel Type V Cas polypeptide systems and compositions for reprogrammable targeting of nucleic acid and polynucleotide components.
The invention features compositions and methods that are useful for determining the fraction of tumor-derived DNA (tumor fraction; TF) in cell free DNA (cfDNA). The methods involve calculating the fraction of tumor-derived DNA in the cfDNA using a combination of copy number alteration data and fragment length distribution data.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
59.
PANCREATIC DUCTAL ADENOCARCINOMA SIGNATURES AND USES THEREOF
Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer death in the United States by 2030. Described herein are pancreatic ductal adenocarcinoma (PDAC) signatures and methods of detecting the same in a sample from a subject. Also described herein, are methods of methods of diagnosing, prognosing, and/or treating PDAC in a subject that can include detecting one or more of the PDAC signatures.
This disclosure is directed to a targeted delivery vehicle that can deliver a cargo to a cell of interest. The targeted delivery vehicle has a fusogen and a targeting domain which are embedded in a lipid bilayer membrane that forms a vesicle, and a cargo within the vesicle. The disclosure is also directed to methods for targeted delivery of cargo using the targeted delivery vehicle described herein.
C07K 14/005 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
61.
CELL-TYPE SPECIFIC TARGETING CONTRACTILE INJECTION SYSTEM
The present disclosure relates generally to the field of delivery systems using contractile injection systems (CIS). Specifically disclosed are engineered extracellular CISs (eCISs) that can deliver non-natural protein payloads to non-natural target cells such as human cells. In addition, methods of using the engineered eCISs are also disclosed.
A61K 47/42 - Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
C07K 14/195 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
TECHNION RESEARCH & DEVELOPMENT FOUNDATION LIMITED (Israel)
Inventor
Priebe, Gregory P.
Kishony, Roy
Chung, Hattie
Schaefers, Matthew M.
Abstract
This disclosure relates to methods and compositions useful for detecting and monitoring low-frequency mutations. Methods cand compositions described herein can be used to guide clinical decisions, for example, by informing on which antibiotics should be avoided, or conversely, should be actively used in the case of compounds that select against a specific type of resistance.
The invention relates to a compound represented by formula (I) or a pharmaceutically acceptable salt thereof, and associated methods of treating cancer.
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/498 - Pyrazines or piperazines ortho- or peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
Disclosed herein are modified mRNAs with poly(A) tails containing one or more additional poly- A tails or 5' caps, which may be made by ligation of nucleic acids onto the 3' terminal end or 5' terminal end of an RNA, respectively. Also provided are compositions comprising one or more modified mRNAs provided herein, and methods of using said compositions for therapeutic or agricultural applications.
Provided herein are compositions, systems, and methods for delivering cargo to a target cell. The compositions, systems, and methods comprise one or more polynucleotides encoding one or more LTR retroelement polypeptides for forming a delivery vesicle and one or more capture moieties for packaging a cargo within the delivery vesicle. The one or more LTR retroelement polypeptides for forming a delivery vesicle may comprise two or more of an LTR retroelement gag protein, a retroelement envelope protein, an LTR retroelement reverse transcriptase, or a combination thereof. The LTR retroelement polypeptide alone, the LTR retroelement envelope protein alone, or both the LTR retroelement-derived polypeptide and LTR retroelement envelope protein may be endogenous.
Provided herein are compositions, systems, and methods for delivering cargo to a target cell. The compositions, systems, and methods comprise one or more polynucleotides encoding one or more LTR retroelement polypeptides for forming a delivery vesicle and one or more capture moieties for packaging a cargo within the delivery vesicle. The one or more LTR retroelement polypeptides for forming a delivery vesicle may comprise two or more of an LTR retroelement gag protein, a retroelement envelope protein, an LTR retroelement reverse transcriptase, or a combination thereof. The LTR retroelement polypeptide alone, the LTR retroelement envelope protein alone, or both the LTR retroelement-derived polypeptide and LTR retroelement envelope protein may be endogenous. In some embodiments the LTR- retroelement-derived polypeptide is a PNMA polypeptide.
The subject matter disclosed herein is generally directed to methods and compositions for a single- or multi-pot protocol for the efficient end to end capture of RNAs (inclusive of their poly- A tail or their 3' end). The invention includes the use of capture oligonucleotides containing a 3' non-extendable end and a selectively cleavable base upstream of an oligo-dT or oligo-dN and a 5' sequence containing unique molecular identifiers, and 2) a deoxyuracil glycosylase that acts only on a deoxyuracil present in a DNA:DNA duplex or DNA/RNA heteroduplex. The invention also includes the use of a dual template switching mechanism..
The invention provides molecular classifiers for use in the characterization and diagnosis of lung cancer and methods of selecting and treating subjects with appropriate personalized cancer treatments, including but not limited to CDK4/6 inhibitors, c-Met inhibitors, PD-1/PD-L1 inhibitors and combinations thereof.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
71.
PARALLEL ANTIBODY ENGINEERING COMPOSITIONS AND METHODS
The present invention discloses high-throughput methods for the creation of antibodies or antigen-binding fragments that can bind to single or multiple targets. Also disclosed are methods for using one or more antibodies or antigen-binding fragments to detect cognate binding partners in various types of samples.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
72.
REPROGRAMMABLE FANZOR POLYNUCLEOTIDES AND USES THEREOF
Systems, methods and composition for targeting polynucleotides are detailed herein. In particular, engineered DNA-targeting systems comprising novel Fanzor polypeptides and a reprogrammable targeting nucleic acid component and methods and application of use are provided.
e.g.in vivoe.g.e.g., virus-like particles) for delivering therapeutic cargos. The present disclosure also provides polynucleotides encoding the lipid-containing particles provided herein, which may be useful for producing said lipid-containing particles. Also provided are methods for editing nucleic acid molecules in cells using the lipid-containing particles provided herein, as well as cells and kits comprising the lipid-containing particles.
C07K 14/005 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
C12N 7/00 - Viruses, e.g. bacteriophages; Compositions thereof; Preparation or purification thereof
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
The present disclosure provides virus-like particles for delivering gene editing agents such as nucleic acid-programmable DNA-binding proteins (napDNAbps) and base editor fusion proteins ("BE-VLPs" or "eVLPs"), and systems comprising such eVLPs. The present disclosure also provides polynucleotides encoding the eVLPs described herein, which may be useful for producing said eVLPs. Also provided herein are methods for editing the genome of a target cell by introducing the presently described eVLPs into the target cell. The present disclosure also provides fusion proteins that make up a component of the eVLPs described herein, as well as polynucleotides, vectors, cells, and kits.
C07K 14/005 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
The present disclosure provides virus-like particles (VLPs) for delivering prime editors, and systems comprising such prime editor (PE) VLPs. The present disclosure also provides polynucleotides encoding the PE-VLPs described herein, which may be useful for producing said PE-VLPs. Also provided herein are methods for editing the genome of a target cell by introducing the presently described PE-VLPs into the target cell. The present disclosure also provides fusion proteins that make up a component of the PE-VLPs described herein, as well as polynucleotides, vectors, cells, and kits.
C07K 14/005 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
Systems, methods and compositions for targeting polynucleotides are detailed herein. In particular, engineered DNA-targeting systems comprising IscB polypeptides, novel IscB nucleases and reprogrammable targeting nucleic acid components and methods and application of use are rovided.
Systems, methods and compositions for targeting polynucleotides are detailed herein. In particular, engineered DNA-targeting systems comprising IsrB polypeptides, novel IsrB nucleases and reprogrammable targeting nucleic acid components and methods and application of use are provided.
Computer-implemented methods, computer program products, and systems determine an omics profiles of a cell using microscopy imaging data. In one aspect, a computer-implemented method determines an omics profiles of a cell using microscopy imaging data by a) receiving microscopy imaging data of a cell or a population of cells; b) determining a targeted expression profile of a set of target genes from the microscopy imaging data using a first machine learning model, the target genes identifying a cell type or cell state of interest; and c) determining a singlecell omics profile for the population of cells using a second machine learning algorithm model. The targeted expression profile and a reference single-cell RNA-seq data set are used as inputs for the second machine learning model.
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
G16H 50/00 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
79.
BIFUNCTIONAL CHIMERIC MOLECULES FOR LABELING OF KINASES WITH TARGET BINDING MOIETIES AND METHODS OF USE THEREOF
112122 are each a linker; and E is an electrophilic reactive group. Molecules according to the present invention find use making substrate modifications such as post-translational modifications to targets that are not the natural substrate of the kinase; accordingly, diseases or disorders may be treated or prevented with molecules of the present disclosure.
C07D 233/58 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring nitrogen atoms
The invention features pseudotyped viral particles (e.g., lentiviral or gammaretroviral particles) and compositions and methods of use thereof, where the viral particles comprise a VHH domain.
C07K 14/155 - Lentiviridae, e.g. human immunodeficiency virus (HIV), visna-maedi virus, equine infectious anaemia virus
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
In vivo approaches for altering cells would benefit from effective methods for retargeting vectors to be specific for particular cell types in a subject. However, such methods remain inefficient and/or poorly developed. Thus, there is a need for improved methods for in vivo delivery of vectors to a target cell. The invention features pseudotyped viral particles (e.g., lentiviral or gammaretroviral particles) and compositions and methods of use thereof, where the viral particles comprise a VHH domain.
C12N 7/04 - Inactivation or attenuation; Producing viral sub-units
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
Compounds, pharmaceutical compositions, and methods of use of said compounds and pharmaceutical compositions for treating or preventing a microbial infection or for inducing antimicrobial activity against a microbial infection.
Aspects of the disclosure relate to Botulinum toxin X (BoNT X) protein variants (e.g., BoNT X protease variants). The variants provided herein have been evolved to cleave procaspase- 1. Some of the variants provided herein do not cleave the native substrate of BoNT X protease, VAMP1 protein. Further aspects of the disclosure relate to nucleic acids encoding the procaspase- 1 cleaving polypeptides described herein and expression vectors comprising the nucleic acids, as well as host cells and fusion proteins comprising the procaspase- 1 cleaving polypeptides described herein and kits comprising the procaspase- 1 cleaving polypeptides, nucleic acids, fusion proteins, expression vectors, or host cells described herein. Further aspects of the disclosure relate to methods of producing BoNT X protein variants (e.g., BoNT X protease variants) and methods of using the BoNT X protein variants (e.g., BoNT X protease variants), for example, to induce cell death.
C07K 14/33 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Clostridium (G)
C12N 15/00 - Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
144 are each independently H, hydroxyl, halogen, lower alkyl or lower alkoxy; as well as related pentamidine analogs and their use to inhibit bacterial growth and treat bacterial infection.
C07C 257/18 - Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to carbon atoms of six-membered aromatic rings
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
A61K 31/444 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/445 - Non-condensed piperidines, e.g. piperocaine
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
C07D 211/22 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulfur atoms by oxygen atoms
C07D 213/60 - Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
C07D 233/64 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
C07D 295/088 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
85.
METHODS AND COMPOSITIONS FOR EDITING A GENOME WITH PRIME EDITING AND A RECOMBINASE
Disclosed are constructs, systems, and methodologies using prime editing (PE), twin prime editing (twinPE), or multi-flap prime editing to carry out site-specific and large-scale genetic modification, such as, but not limited to, insertions, deletions, inversions, replacements, and chromosomal translocations of whole or partial genes (e.g., whole gene, gene exons and/or introns, and gene regulatory regions). In certain embodiments, the disclosure provides constructs, systems, and methods using prime editing (PE), e.g., single flap or "classical" PE or twinPE or multi-flap PE, to install one or more target sites for site specific recombination in a target genomic locus (e.g., a specific gene, exon, intron, or regulatory sequence), which may then be acted on by one or more site-specific recombinases to effectuate a large-scale genetic modification, such as an insertions, deletions, inversions, replacements, and chromosomal translocations.
The subject matter disclosed herein is generally directed to compositions and methods for multiplex decoding of quadruplet codons and methods for increasing the efficiency of quadruplet codon decoding using qtRNA evolution. Continuous evolution of qtRNAs is disclosed. Multiplex qtRNA constructs are disclosed.
Recent advances in the understanding of two CRISPR-Cas systems, namely, Type VI (Cas13a-d) and Type III (Type III-A-B), have shown both of them to have the ability to efficiently target RNA. Provided herein are compositions and methods for trans-splicing precursor mRNA using a catalytically-inactive Cas protein (dCas) and a trans-splicing construct comprising a guide RNA, an intron, a splice acceptor, donor RNA, and a poly A tail. The dCas is capable of forming a complex with the guide RNA and directing sequence-specific binding of the complex to a target precursor mRNA for genetic modification and any polypeptides derived thereof. The technology has important potential therapeutic applications such as correcting genetic mutations through exon replacement, insertion of transgenes, and increasing gene expression, and in non-therapeutic applications such as cell- and tissue-specific diagnostics.
C12N 15/63 - Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
88.
SYSTEMS AND METHODS FOR ASSESSMENT OF BODY FAT COMPOSITION AND TYPE VIA IMAGE PROCESSING
The subject matter disclosed herein relates to utilizing the silhouette of an individual to measure body fat volume and distribution. Particular examples relates to providing a system, a computer-implemented method, and a computer program product to utilize a binary outline, or silhouette, to predict the individual's fat depot volumes with machine learning models.
Described in several exemplary embodiments are compositions including a targeting moiety effective to target a central nervous system cell and formulations thereof. In certain embodiments, the targeting moiety is composed of one or more n-mer inserts, that can include one or more RGD motifs, and/or one or more P-motifs. Also described in certain example embodiments are vector systems configured to generate polypeptides containing the one or more targeting moieties. Also described herein are methods of generating a targeting moiety effective to target a central nervous system cell and using the compositions containing the targeting moieties described herein, such as to deliver a cargo to a subject and/or treat a central nervous system disease, disorder, or system thereof.
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
A61P 9/02 - Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
C07K 7/06 - Linear peptides containing only normal peptide links having 5 to 11 amino acids
Disclosed are methods and compositions for treating CTNNB1 syndrome. The disclosed methods and compositions may utilize or comprise a glycogen synthase kinase 3 (GSK3) inhibitor, or a pharmaceutically acceptable salt thereof. The GSK3 inhibitor may comprise small molecules such as substituted tricyclic pyrazolo-tetrahydroquinolinones, and the GSK3 inhibitor may selectively inhibit GSK3β and GSK3α or dually inhibit GSK3α and GSK3β.
A61K 31/4745 - Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
C07D 471/02 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups in which the condensed system contains two hetero rings
THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK (USA)
THE BROAD INSTITUTE, INC. (USA)
PRESIDENT AND FELLOWS OF HARVARD COLLEGE (USA)
Inventor
Quinn, Peter M.J.
Lopes Da Costa, Bruna
Tsang, Stephen H.
Liu, David R.
Abstract
The present disclosure provides systems, methods, and compositions for modifying the crumbs homologue-1 gene. Particularly the present disclosure provides systems, methods, and compositions for prime editing insertion or correction of mutations in the crumbs homologue-1 gene. Modifying crumbs homologue-1 includes a Cas protein, reverse transcriptase, RNA polynucleotides, and an extension sequence comprising a primer binding sequence (PBS) and a reverse transcriptase template (RTT) sequence.
Disclosed herein are methods and devices for use in early detection of Richter's Syndrome. The methods include sequencing a panel of regions in cell-free DNA molecules and detecting one or more markers that are indicative of Richter's Syndrome.
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
Described in several exemplary embodiments are compositions including a targeting moiety effective to target a central nervous system cell and formulations thereof. In certain embodiments, the targeting moiety is composed of a n-mer insert containing or being composed only of a P-motif. Also described in certain example embodiments are vector systems configured to generate polypeptides containing the one or more targeting moieties. Also described herein are methods of generating a targeting moiety effective to target a central nervous system cell and using the compositions containing the targeting moieties described herein, such as to deliver a cargo to a subject and/or treat a central nervous system disease, disorder, or system thereof.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
C07K 14/005 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
Provided herein are methods and compositions related to the treatment or prevention of vascular disease and/or heart disease using biomarkers of ADAMTS7 activity and antagonists of ADAMTS7.
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase involving peptidase or proteinase
G01N 33/96 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood or serum control standard
Described in several exemplary embodiments are compositions including a targeting moiety effective to target a central nervous system cell and formulations thereof. In certain embodiments, the targeting moiety is composed of one or more n-mer inserts, that can include one or more RGD motifs, and/or one or more P-motifs. Also described in certain example embodiments are vector systems configured to generate polypeptides containing the one or more targeting moieties. Also described herein are methods of generating a targeting moiety effective to target a central nervous system cell and using the compositions containing the targeting moieties described herein, such as to deliver a cargo to a subject and/or treat a central nervous system disease, disorder, or system thereof.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
96.
TUMOR AVATAR VACCINE COMPOSITIONS AND USES THEREOF
Disclosed herein are methods of eliciting an anti-cancer immune response by administering tumor-associated antigens, cells containing tumor-associated antigens, and/or nucleic acids encoding tumor-associated antigens, inducing immunogenic cell death in the cells expressing or containing the tumor-associated antigens, and optionally generating hyperactivated dendritic cells. Expression of tumor-associated antigens in a separate anatomical site generates a tumor avatar, which mimics the antigenic, but not immunosuppressive, environment of the tumor, with the generation of hyperactivated dendritic cells enhancing antigen presentation to elicit a robust anti-tumor T cell and antibody response. Also provided are compositions and kits containing nucleic acids and other components for use in the methods provided herein.
The present disclosure provides methods, compositions, and systems for profiling epitranscriptomic RNA modifications in a cell. The present disclosure also provides methods for profiling interactions between one or more RNAs of interest in a cell and an RNA-binding protein (e.g., a protein that introduces an epitranscriptomic modification on an RNA of interest). Also provided by the present disclosure are methods for diagnosing a disease or disorder in a subject based on a profile of epitranscriptomic RNA modifications or a profile of interactions between an RNA binding protein and RNAs in a cell, including cells within an intact tissue. Methods of screening for or testing a candidate agent capable of modulating epitranscriptomic modification of one or more RNAs or interactions between one or more RNAs and an RNA-binding protein are also provided by the present disclosure. The present disclosure also provides methods for treating a disease or disorder in a subject in need thereof. Pairs of probes and sets of probes comprising oligonucleotide portions, which may be useful for performing the methods described herein, are also described by the present disclosure. Additionally, the present disclosure provides kits comprising any of the probes described herein.
C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
98.
RIBOSOMAL RNA (RRNA) VARIANTS POSSESSING ENHANCED PROTEIN PRODUCTION CAPABILITIES
The present disclosure relates to compositions, methods and kits for enhancing ribosomal activities in a host cell, especially improvement of the translation activity of heterologous ribosomes within a host cell. Specifically, the instant disclosure provides a number of evolved rRNA sequences, which were remarkably identified to possess enhanced translation activities, improved orthogonal-ribosome binding site (o-RBS) and orthogonal anti-ribosome binding site (o-antiRBS) sequences, host cells possessing deletion or disruption of ribosome hibernation promoting factor (HPF) that thereby exhibit enhanced propagation of selection phage constructs during (PACE), among other aspects. New transgenic organisms harboring heterologous ribosomes and operons are also provided.
Described herein are muscle-specific targeting moieties and compositions including the muscle specific targeting motifs. Also described herein are uses of the muscle-specific targeting motifs and compositions including the muscle specific targeting moieties. In some embodiments, the muscle-specific targeting moieties and compositions including the muscle specific targeting moieties can be used to direct delivery of a cargo to a muscle cell.
The present disclosure provides compositions and methods for prime editing with improved editing efficiency and/or reduced indel formation with modified prime editors and prime editor fusion proteins. The disclosure further provides, vectors, cells, and kits comprising the compositions and polynucleotides of the disclosure.
patents
