47 results about "Trypsin deficiency" patented technology

Among other things, the present disclosure provides designed oligonucleotides and compositions thereof. In some embodiments, oligonucleotides and compositions of the present disclosure can provide high levels of adenosine editing. In some embodiments, oligonucleotides and compositions of the present disclosure are useful for treating various conditions, disorders or diseases, e.g., alpha-1 antitrypsin deficiency. In some embodiments, the present disclosure provides methods for treating various conditions, disorders or diseases that can benefit from adenosine editing.

Compositions and methods for introducing double-stranded breaks within the SERPINA1 gene are provided. Compositions and methods for reducing and eliminating mutant forms of α1-antitrypsin (AAT), such as seen in subjects having α1-antitrypsin deficiency (AATD), are provided.

The present invention relates to a nucleic acid that encodes both an Alpha-1 antitrypsin (A1AT or AAT) protein and an RNA molecule able to inhibit the expression of an endogenous A1AT protein. The invention further relates to associated expression cassettes, recombinant adeno-associated virus (rAAV) vectors, promoters, pharmaceutical compositions and kits for use in the treatment of Alpha-1 antitrypsin deficiency (A1ATD or AATD).

Compositions and methods for expressing alpha 1 antitrypsin (AAT) in a host cell are provided. Also provided are compositions and methods for treating subjects having alpha 1 antitrypsin deficiency (AATD).

Described are methods for treating alpha-1 antitrypsin deficiency (AATD) in a human patient in need of treatment, using pharmaceutical compositions that include AAT RNAi agents. The pharmaceutical compositions disclosed herein that include AAT RNAi agents, when administered to a human patient in need thereof, treat liver diseases associated with AAT deficiency such as chronic hepatitis, cirrhosis, increased risk of hepatocellular carcinoma, transaminitis, cholestasis, fibrosis, fulminant hepatic failure, and other liver-related diseases.

The present disclosure provides methods of large-scale preparation of alpha-1 antitrypsin (AAT) activity modulators useful for treating alpha-1 antitrypsin deficiency (AATD), such as 4-(5-(4-fluorophenyl)-6-(tetrahydro-2H-pyran-4-yl)-1,5-dihydropyrrolo[2,3-f]indazol-7-yl)benzoic acid (Compound 1), 3-[5-(4-fluorophenyl)-6-isopropyl-1H-pyrrolo[2,3-f]indazol-7-yl]propanoic acid (Compound 2), or any pharmaceutically acceptable salt of any of the foregoing.

The present invention relates to a novel method of treating pulmonary emphysema in patients suffering from alpha-1 antitrypsin deficiency (AATD), a genetic disorder that causes low levels of alpha-1 antitrypsin (AAT), a protein that protects the lungs from damage by neutrophil elastase. The invention consists of aerosolizing nanoparticles composed of apolipoprotein A1 enriched with AAT (A1NP). The invention aims to deliver these nanoparticles directly to the lungs, where they can interact with the alveolar surface and modulate the inflammatory and proteolytic processes that lead to emphysema. In particular, the inventors report that said nanoparticles are not cytotoxic, have anti-inflammatory and anti-elastase properties, can cross alveolar epithelial cells, and are not immunogenic in mice.

The present invention provides a method for preparing an siRNA for treating α1-antitrypsin deficiency. The siRNA is Fazirsiran. Fazirsiran is a double-stranded RNA composed of a complementarily paired sense strand and antisense strand. The preparation method comprises: mixing sense strand substrates, antisense strand substrates, and an RNA ligase, and using the RNA ligase to catalyze the linkage between the sense strand substrates and between the antisense strand substrates by means of phosphodiester bonds, to obtain a sense strand and an antisense strand, thereby obtaining Fazirsiran, wherein the sense strand substrates can form the sense strand, and the antisense strand substrates can form the antisense strand. Compared with the preparation of Fazirsiran by means of chemical synthesis, the product obtained by the preparation method of the present application has higher purity and fewer impurities, and the reaction conditions are mild, facilitating industrial large-scale production.

The present invention relates to compositions, methods and kits for the treatment or prevention of obstructive pulmonary disease, associated with or caused by alpha-1 antitrypsin deficiency. In one aspect, the present invention provides method of treating or preventing obstructive pulmonary disease, associated with or caused by alpha-1 antitrypsin deficiency in a subject in need thereof, the method comprising administering to the subject an antisense oligonucleotide (AON) that promotes the production of endogenous soluble RAGE, thereby treating or preventing obstructive pulmonary disease, associated with or caused by alpha-1 antitrypsin deficiency in a subject.

Among other things, the present disclosure provides various technologies including chirally controlled oligonucleotide compositions and technologies for manufacturing and using such oligonucleotide compositions. In some embodiments, the present disclosure provides technologies useful for editing of adenosine in transcripts, e.g., SERPINA1 transcripts. In some embodiments, the present disclosure provides methods for treating various conditions, disorders or diseases that can benefit from adenosine editing. In some embodiments, the present disclosure provides technologies useful for preventing or treating various conditions, disorders or diseases, e.g., alpha-1 antitrypsin deficiency.

The invention relates to specified carboxylic acid compounds of formula (1), and pharmaceutical compositions containing the compounds. The compounds may be inducers of α1-antitrypsin (A1AT) and may be used in the treatment of a disease or disorder such as α1-antitrypsin deficiency (A1AD or AATD).

Disclosed in the present invention are a polymorph of a benzo[c]chroman compound, a preparation method therefor and use thereof. The present invention particularly provides a polymorph of a compound represented by formula I, a preparation method therefor and use thereof. The compound represented by formula I is used as a cathepsin C inhibitor, and a crystalline form of the compound and a pharmaceutical composition comprising the crystalline form can be used for treating asthma, obstructive pulmonary diseases, bronchiectasis, ANCA-related vasculitis, psoriasis, α1-antitrypsin deficiency, lupus nephritis, diabetes, inflammatory bowel diseases, rheumatic arthritis, rhinosinusitis, hidradenitis suppurativa or cancers.

A number of medical disorders are caused by either an insufficiency of a gene product or a defective gene product. Gene therapy can be used to provide a sufficient amount of a gene product when a disorder is caused by an insufficiency and can also be used to inactivate genes that produce defective gene products. Examples of disorders that can be treated by providing a sufficient amount of a gene product include lysosomal storage diseases, clotting disorders, diabetes, and alpha-1 antitrypsin deficiency. Systems and methods to produce B cells that express selected antibodies and gene products are described. The systems and methods can be used to provide prolonged and tunable expression of the gene products for the treatment of diseases such as lysosomal storage diseases, clotting disorders, diabetes, or other protein deficiencies.

Disclosed are polymorphs of benzo[c]chromane compounds, and preparation methods and uses thereof, and specifically provided are polymorphs of a compound shown in formula I, and preparation methods and uses thereof. The compound shown in formula I is a cathepsin C inhibitor, and the crystal form and the pharmaceutical composition containing the crystal form can be used for treating asthma, obstructive pulmonary disease, bronchiectasis, ANCA-associated vasculitis, psoriasis, alpha 1-antitrypsin deficiency, lupus nephritis, diabetes, inflammatory bowel disease, rheumatoid arthritis, sinusitis, hidradenitis suppurativa or cancer.

The present disclosure is generally directed to tetracyclic analogs that modulate autophagy in a subject suffering from alpha-1 antitrypsin deficiency (ATD) and possibly other autophagy associated diseases or disorders, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis.

This refers to RNAI agents for inhibiting the expression of the alpha-1 antitrypsin (aat) gene, compositions including Aat RNAI agents, and methods of use. Pharmaceutical compositions including one or more Aat RNAI agents together with one or more excipients capable of delivering the RNAI agents to a liver cell in vivo are also disclosed. Delivery of Aat RNAI agents to liver cells in vivo inhibits Aat gene expression and treats diseases associated with Aat deficiency such as chronic hepatitis, cirrhosis, hepatocellular carcinoma, transaminitis, cholestasis, fibrosis, and fulminant hepatic failure.

This disclosure provides large-scale processes for preparing a modulator of alpha-1 antitrypsin (AAT) activity that may be useful for treating alpha-1 antitrypsin deficiency (AATD), such as 4-(5-(4-fluorophenyl)-6-(tetrahydro-2H-pyran-4-yl)-1,5-dihydropyrrolo[2,3-f]indazol-7-yl)benzoic acid (Compound 1), 3-[5-(4-fluorophenyl)-6-isopropyl-1H-pyrrolo[2,3-f]indazol-7-yl]propanoic acid (Compound 2), or a pharmaceutically acceptable salt of any of the foregoing.

To provide a method of treating patients with alpha-1 anti-trypsin deficiency that addresses both lung pathology and liver toxicity.SOLUTION: The present invention features compositions and methods for editing deleterious mutations associated with alpha-1 anti-trypsin (A1AT) deficiency. In particular embodiments, the invention provides methods for correcting mutations in an A1AT polynucleotide using an adenosine deaminase base editor, ABE8, having unprecedented levels of efficiency.SELECTED DRAWING: Figure 1

The disclosure provides, e.g., compositions, systems, and methods for targeting, editing, modifying, or manipulating a host cell's genome at one or more locations in a DNA sequence in a cell, tissue, or subject. Gene modifying systems for treating alpha- 1 antitrypsin deficiency (AATD) are described. Improved gRNA scaffolds compatible with St1Cas9 are also described.

The disclosure provides, e.g., compositions, systems, and methods for targeting, editing, modifying, or manipulating a host cell's genome at one or more locations in a DNA sequence in a cell, tissue, or subject. Gene modifying systems for treating alpha- 1 antitrypsin deficiency (AATD) are described. Improved gRNA scaffolds compatible with St1Cas9 are also described.

Compositions and methods for editing detrimental mutations associated with alpha 1 antitrypsin deficiency (A1AD). In particular embodiments, the present invention provides methods for the treatment of A1AD using a modified adenosine base editor with improved in-target editing and reduced off-target editing to correct mutations associated with A1AD.

Provided herein are humanized rodent models comprising a human SERPINA1 transgene, optionally wherein the rodents develop Alpha- 1 antitrypsin deficiency (A1ATD). Further provided herein are methods related to the use of the humanized rodent models for screening therapeutic efficacy for A1ATD, for example, for screening the efficacy of any treatment selected from the group consisting of liver transplantation, respiratory agents, purified alpha- 1 antitrypsin (A1AT) protein, and gene therapy.

A pharmaceutically acceptable salt of a benzo[c]chroman compound and a polymorphic form and use of the pharmaceutically acceptable salt. The pharmaceutically acceptable salt is selected from hydrochloride, methanesulfonate, phosphate, L-tartrate, maleate, p-toluenesulfonate, sulfate, fumarate, succinate, citrate, malate, and hydrobromide. The pharmaceutically acceptable salt and the polymorphic form thereof improve the bioavailability and the stability, and as a cathepsin C inhibitor, can be used for treating asthma, obstructive pulmonary disease, bronchiectasis, ANCA-associated vasculitis, psoriasis, α1-antitrypsin deficiency, lupus nephritis, diabetes, inflammatory bowel disease, rheumatoid arthritis, sinusitis, hidradenitis suppurativa, or cancer.

7- or 8-hydroxy-isoquinoline and 7- or 8-hydroxy-quinoline derivatives as alpha-1-antitrypsin modulators for treating alpha-1-antitrypsin deficiency (AATD).

This disclosure provides compositions and methods for the editing of a SERPINA1 gene with prime editing.