13715results about "Genetic material ingredients" patented technology

Described herein, inter alia, are GTPase inhibitors and uses thereof.

To provide methods for treating a subject having or at risk of developing a neurocognitive disorder, such as frontotemporal lobar degeneration or neuronal ceroid lipofuscinosis.SOLUTION: Provided is a method comprising administering, to a subject diagnosed as having a neurocognitive disorder (NCD), a composition comprising a population of cells comprising a transgene encoding a progranulin (PGRN) or a granulin (GRN).SELECTED DRAWING: Figure 1A

The invention provides stabilizing agents, compositions, methods of manufacturing, and uses thereof. In one aspect, a lipid nanoparticle composition includes: (a) an ionizable lipid; (b) two or more lipids; and (c) a stabilizing agent of formula (I) or formula (II) and methods for preparing the stabilizing agents and the lipid nanoparticle are provided.

Aspects of the disclosure relate to complexes and other aspects relate to formulations (e.g., aqueous, lyophilized forms) comprising such complexes comprising an oligonucleotide (e.g., an RNAi oligonucleotide such as an siRNA, useful for targeting DUX4) covalently linked to an antibody (e.g., anti-TfRl antibody).

The invention provides a rapidly metabolized lipid compound, and particularly relates to a compound as shown in formula (I), or pharmaceutically acceptable salt, isotope variant, tautomer or stereoisomer thereof. The invention also provides nanoparticle pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions thereof in delivery of nucleic acids. # imgabs0 #

Aspects of the disclosure relate to methods of reducing fatigue in a subject having myotonic dystrophy type 1 (DM1). Aspects of the disclosure relate to methods of treating one or more symptoms assessable by the MDHI (e.g., a GI symptom, myotonia, upper extremity function impairment, fatigue, mobility impairment, impairment in the ability to perform activities, pain, vision impairment, communication impairment, sleep impairment, emotional issues, cognitive impairment, social satisfaction impairment, social performance impairment, breathing impairment, swallowing impairment, and / or hearing impairment) in a subject having myotonic dystrophy type 1 (DM1). In some embodiments, the methods comprise administering to the subject a composition comprising complexes (e.g., muscle targeting complexes) comprising an oligonucleotide (e.g., a DMPK- targeting oligonucleotide) covalently linked to an antibody (e.g., anti-TfRl antibody).

The invention provides stabilizing agents, compositions, methods of manufacturing, and uses thereof. In one aspect, a lipid nanoparticle composition including: (a) an ionizable lipid; (b) two or more lipids; and (c) a stabilizing agent of formula (I) and a method for preparing the stabilizing agent and the lipid nanoparticle are provided.

The invention provides stabilizing agents, compositions, methods of manufacturing, and uses thereof. In one aspect, a lipid nanoparticle composition includes: (a) an ionizable lipid; (b) two or more lipids; and (c) a stabilizing agent of formula (I) and a method for preparing the stabilizing agent and the lipid nanoparticle are provided.

Compounds are provided having the following structure:or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R1a, R1b, R2a, R2b, R3a, R3b, R4a, R4b, R5, R6, R7, R8, R9, L1, L2, a, b, c, d and e are as defined herein. Use of the compounds as a component of lipid nanoparticle formulations for delivery of a therapeutic agent, compositions comprising the compounds and methods for their use and preparation are also provided.

Among other things, the present disclosure provides oligonucleotide compositions and methods thereof. In some embodiments, the present disclosure provides structural elements including various chemical modifications of sugars, nucleobases and / or internucleotidic linkages that are useful for adenosine editing. In some embodiments, the present disclosure provides methods for preventing or treating conditions, disorders or diseases that can benefit from editing of an adenosine in a nucleic acid.

The present disclosure describes improved LNP-based RNA vaccines, nucleobase editing systems, and therapeutics for use in treating and / or immunization against disease. In particular, the disclosure describes improved LNPs, including novel and improved ionizable lipids for making LNPs, that enhance the targeted delivery of LNP-based RNA vaccines and therapeutics based on linear and / or circular mRNAs. The improved LNPs protect linear and / or circular mRNA payloads from degradation and clearance while achieving targeted systemic or local delivery for use as enhanced vaccines and / or therapeutic agents.

Among other things, the present disclosure provides oligonucleotide compositions and methods thereof. In some embodiments, oligonucleotides comprise various chemical modifications of sugars, nucleobases, and / or internucleotidic linkages and patterns thereof and are useful for exon skipping. In some embodiments, the present disclosure provides technologies useful for skipping exon 52 of dystrophin (DMD) transcripts. In some embodiments, the present disclosure provides technologies useful for modulating DMD transcript splicing. In some embodiments, the present disclosure provides methods for preventing or treating conditions, disorders or diseases including Duchenne muscular dystrophy.

The invention relates to retrieving or modifying target nucleic acids, such as host cell chromosomal DNA, by homologous recombination with vectors that have been cut to provide recombinogenic nucleic acid strands in situ. The methods described herein can be used to modify a target nucleic acid in vitro or in any prokaryotic or eukaryotic cell using homologous recombination.

Disclosed are compositions of lipid nanoparticles (LNP) comprising an ionizable cationic lipid, a phospholipid, a sterol, and a PEG-lipid (non-functionalized and optionally functionalized). The functionalized PEG-lipid can be conjugated with a binding moiety to create a targeted LNP (tLNP). The disclosed tLNP preferentially deliver a nucleic acid molecule or other negatively charged payload to cells expressing a cell surface antigen recognized by the binding moiety of the tLNP, and are better tolerated, as compared to LNPs and tLNPs comprising ionizable cationic lipids found in marketed pharmaceuticals comprising LNPs.

Among other things, the present disclosure provides oligonucleotide compositions and methods thereof. In some embodiments, oligonucleotides comprise various chemical modifications of sugars, nucleobases, and / or intemucleotidic linkages and patterns thereof and are useful for exon skipping. In some embodiments, the present disclosure provides technologies useful for skipping exon 45 of dystrophin (DMD) transcripts. In some embodiments, the present disclosure provides technologies useful for modulating DMD transcript splicing. In some embodiments, the present disclosure provides methods for preventing or treating conditions, disorders or diseases including Duchemie muscular dystrophy.

Disclosed are compositions of lipid nanoparticles (LNP) comprising an ionizable cationic lipid, a phospholipid, a sterol, and a PEG-lipid (non-functionalized and optionally functionalized). The functionalized PEG-lipid can be conjugated with a binding moiety to create a targeted LNP (tLNP). The disclosed tLNP preferentially deliver a nucleic acid molecule or other negatively charged payload to cells expressing a cell surface antigen recognized by the binding moiety of the tLNP, and are better tolerated, as compared to LNPs and tLNPs comprising ionizable cationic lipids found in marketed pharmaceuticals comprising LNPs.

Provided herein are engineered nucleic acids (e.g., expression vectors, including viral vectors, such as lentiviral vectors, adenoviral vectors, AAV vectors, herpes viral vectors, and retroviral vectors) that encode OCT4; KLF4; SOX2; or any combination thereof that are useful, for example, in inducing cellular reprogramming, tissue repair, tissue regeneration, organ regeneration, reversing aging, or any combination thereof. Also provided herein are recombinant viruses (e.g., lentiviruses, alphaviruses, vaccinia viruses, adenoviruses, herpes viruses, retroviruses, or AAVs) comprising the engineered nucleic acids (e.g., engineered nucleic acids), engineered cells, compositions comprising the engineered nucleic acids, the recombinant viruses, engineered cells, engineered proteins, chemical agents that are capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, an engineered protein selected from the group consisting of OCT4; KLF4; SOX2; or any combination thereof, an antibody capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, and methods of treating a (e.g., ocular disease), preventing a disease (e.g., ocular disease), regulating (e.g., inducing or inducing and then stopping) cellular reprogramming, regulating tissue repair, regulating tissue regeneration, or any combination thereof).

The present disclosure relates to cationic and / or ionizable lipids and nucleic acid-lipid particle compositions comprising the same. The present disclosure also relates to methods of using and delivering the described lipids and lipid-containing particles.

The invention discloses brain-targeted stem cell membrane bionic cationic liposome as well as a preparation method and application thereof. The preparation method comprises the following steps: extracting and purifying to obtain a stem cell membrane; preparing a cationic liposome; the stem cell membrane and the cationic liposome are fused to obtain the stem cell membrane bionic cationic liposome, and the relative dosage of the stem cell membrane and the cationic liposome is that the mass ratio of the total protein mass of the stem cell membrane to the total fat mass of the cationic liposome is 1: (2-24). The stem cell membrane bionic cationic liposome constructed by using the purified stem cell membrane has high brain targeting ability, low immune irritation and efficient nucleic acid drug carrying ability, can break through the blood brain barrier, realizes efficient targeting delivery of nucleic acid drugs to cells of the brain including neurons, and has good application prospects. Particularly, the polypeptide can be used as a targeted delivery platform of nucleic acid drugs for targeted therapy of cerebral diseases, especially cerebral arterial thrombosis.

Among other things, the present disclosure provides oligonucleotide compositions and methods thereof. In some embodiments, the present disclosure provides technologies useful for exon skipping in cell populations, e.g., myocyte stem cells. In some embodiments, the present disclosure provides technologies useful for restoring functioning of myocyte stem cells. In some embodiments, the present disclosure provides technologies useful for regeneration of myocyte stem cells. In some embodiments, the present disclosure provides technologies useful for differentiation of myocyte stem cells. In some embodiments, the present disclosure provides methods for preventing or treating conditions, disorders, or diseases including Duchenne muscular dystrophy.

The invention relates to antisense oligonucleotides that can form a double stranded nucleic acid complex with a target RNA molecule, wherein the double stranded nucleic acid complex is capable of recruiting an adenosine deaminating enzyme for deamination of a target adenosine in the target RNA molecule, wherein the nucleotide in the AON that is directly opposite the target adenosine comprises a 2',2'-disubstitution, preferably a 2',2'-difluro substitution in the ribose moiety.

Provided herein are lipids having the Formula I or Formula Ia:and pharmaceutically acceptable salts thereof, wherein R′, R1, R2, R3, R4, R5, R6a, R6b, X1, X2, and n are as defined herein for Formula I and Formula Ia, respectively. Also provided herein are lipid nanoparticle (LNP) compositions comprising lipid having the Formula I or Ia and a capsid-free, non-viral vector (e.g., ceDNA). In one aspect of any of the aspects or embodiments herein, these LNPs can be used to deliver a capsid-free, non-viral DNA vector to a target site of interest (e.g., cell, tissue, organ, and the like).

The disclosure relates to compositions and methods for modulating, e.g., reducing or eliminating, the expression of ATXN2 via delivery using an adeno-associated viral (AAV) capsid variant. The compositions and methods of the present disclosure are useful in the treatment of subjects diagnosed with, suspected of having, or having spinocerebellar ataxia type 2 (SCA2) or another ATXN2-related disorder.

Compounds are provided having the following structure:or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, wherein a, b, c, d, G1, G2, L1, L2, R1a, R1b, R2a, R2b, R3a, R3b, R4a, R4b, R5, R6, R7, R8 and X are as defined herein. Use of the compounds as a component of lipid nanoparticle formulations for delivery of a therapeutic agent, nanoparticles comprising the compounds and methods for their use and preparation are also provided.

The invention relates to the technical field of biological medicines, and provides application of an ADRM1 inhibitor in preparation of a medicine for treating osteoporosis. Through the scheme of the invention, the ADRM1 affects bone metabolism, bone tissue morphological structure and osteoporosis progress, and can provide a new drug target for clinical prevention and treatment of osteoporosis. The ADRM1 inhibitor is applied to preparation of the osteoporosis medicine, and bone mass loss can be obviously reduced by down-regulating ADRM1 expression or inhibiting ADRM1 activity and inhibiting differentiation and functions of osteoclasts, so that the effect of treating osteoporosis is achieved.

The disclosure relates to compositions and methods for, inter alia, altering, e.g., enhancing, the level of GBA1 protein via delivery using an adeno-associated viral (AAV) capsid variant. The compositions and methods of the present disclosure are useful, inter alia, for the treatment of subjects who have, have been diagnosed with having, or are at risk of having a GBA1-related disorder, e.g., Parkinson's Disease (PD), Gaucher Disease (GD), Dementia with Lewy Bodies (DLB), or Lewy Body Dementia (LBD).

Among other things, the present disclosure provides oligonucleotides, compositions and methods thereof that can bring about specific editing of a target adenosine in a target RNA molecule. Such oligonucleotides, compositions and methods are useful to treat, prevent, or ameliorate MECP2 associated disorders, diseases and syndromes that can benefit from adenosine modification.

The invention provides a production strain of an antibiotic-free plasmid, the production strain is a gene editing strain of a PIR strain and is named as PIR1-WN:: 0636 or PIR1-PR: 0636, the production strain contains a nucleotide sequence for coding toxin protein and the antibiotic-free plasmid, and the antibiotic-free plasmid contains a nucleotide sequence for coding antitoxin protein; and preferably, the replicon DNA element of the nonreactive plasmid is R6K-gamma. The toxin protein gene of the production strain disclosed by the invention can be stably passaged, has lethality after being induced and can be used for plasmid screening; according to the invention, the positive rate of transforming the nonreactive plasmid into the PIR1-WN:: 0636 strain is more than 80%, and stable production of the plasmid with a high superhelix ratio can be realized.

The invention relates to retrieving or modifying target nucleic acids, such as host cell chromosomal DNA, by homologous recombination with vectors that have been cut to provide recombinogenic nucleic acid strands in situ. The methods described herein can be used to modify a target nucleic acid in vitro or in any prokaryotic or eukaryotic cell using homologous recombination.