Described herein are compositions and methods for treating Friedreich's Ataxia (FA) using adeno-associated virus (AAV) to deliver therapeutics agents.

This invention relates to polynucleotides comprising optimized aspartylglucosaminidase (AGA) open reading frames and vectors and cells comprising the same. The invention further relates to methods of using the same for delivery of the open reading frame to a cell or a subject and methods for treating aspartylglucosaminuria (AGU) in a subject.

A method for treating a metabolic disorder associated with abnormal bodyweight in a subject is provided, the method including administering to the subject an effective amount of a compound that modulates phosphatidylinositol 5-phosphate 4-kinase beta (PI5P4Kβ) activity, wherein a PI5P4Kβ inhibitor is administered when the subject suffers from a metabolic disorder associated with an underweight bodyweight; and wherein a PI5P4Kβ agonist is administered when the subject suffers from a metabolic disorder associated with an overweight or obese bodyweight. Also provided herein are methods of increasing meat quality and/or yield in livestock or domesticated poultry by administering to an animal an effective amount of a PI5P4Kβ inhibitor, and genetically engineered animals having a substitution in PI5P4Kβ that reduces its GTP-sensing activity.

The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues or organ which are targeted as sites for delivery. Also provided are vectors and vector systems some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.

This invention relates to selective inhibition of the alternative pathway (AP) of the complement system using an anti-factor D antibody. Specifically, the invention relates to methods of treating an AP-mediated disease or AP-mediated disorder in an individual by contacting the individual with an anti-factor D antibody.

Compositions and methods for editing, e.g., introducing double-stranded breaks, within the TTR gene in combination with administration of a corticosteroid are provided. Compositions and methods for treating subjects having amyloidosis associated with transthyretin (ATTR), in which a guide RNA and a corticosteroid are administered, are provided.

Disclosed are Pear 1 and, serving as a target of fibrotic diseases, applications in a medicament for treating human Pear 1-related diseases. Also disclosed are a Pear 1-targeting antibody or a mutant of same or a composition comprising same and applications thereof. Disclosed are a humanized Pear 1 transgenic mice model, a construction method for same, and applications thereof. The technical solution of the present invention regulates fibroblast activation and has broad application prospects in treating fibrotic diseases and accompanying debilitating diseases.

The disclosure provides a dual-vector intein-mediated protein trans-splicing system, cells, compositions, and methods of using the same for gene therapy. In some embodiments, the disclosure provides methods and compositions for treating an autosomal recessive type of non-syndromic deafness, DFNB16, by delivering a STRC gene, encoding a STRC protein, using the dual-vector system described herein.

The present disclosure generally relates to compositions and methods of use thereof for treating heart failure encompassing administering a composition of modified mRNA (modRNA) encoding for type 2 phosphatidylinositol-5-phosphate 4-kinase gamma (pip4k2c) to heart tissue of a subject in need thereof.

Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized TTR locus and methods of using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized TTR locus express a human transthyretin protein or a chimeric transthyretin protein, fragments of which are from human transthyretin. Methods are provided for using such non-human animals comprising a humanized TTR locus to assess in vivo efficacy of human-TTR-targeting reagents such as nuclease agents designed to target human TTR. Methods are also provided for making such non-human animals comprising a humanized TTR locus.