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.

The present disclosure provides methods and compositions for transferring a gene encoding sphingosine-1-phosphate lyase (SPL) in a subject in need thereof by using recombinant AAV virions. The subject may have or may develop SPL insufficiency syndrome (SPLIS). The subject may be identified on the basis of a genetic test and/or SPLIS symptoms. The methods and compositions are also useful in lowering circulating sphingosine-1-phosphate levels in a subject having elevated S1P levels.

The invention discloses methods for the generation of chimaeric human—non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising said antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in said methods.

The present invention provides a method of lowering blood pressure in a subject, comprising genetically modifying a myosin phosphatase target subunit (Mypt1) gene in a vascular smooth muscle cell of the subject, whereby the genetic modification of Mypt1 results in a deletion or inactivation of exon 24. The invention further provides vectors, host cells, and compositions useful for carrying out the methods of the invention.

The present invention pertains to a non-human genetically modified animal with increased susceptibility to infection with a human virus. The invention suggests to genetically impair the expression of newly identified viral infection repression factors CD302, Cr11, Ndufc2, AW112010, Scarb2 and Zc3hav1, which markedly improves infection with human viruses in none-human hosts. Furthermore provided are methods for the generation of the animal of the invention, methods for increasing or reducing the susceptibility of a cell to viral infection, methods for screening novel modulators of viral infection as well as new therapy options for the treatment of viral diseases, in particular hepatitis C.

The present disclosure provides, among other aspects, codon-altered polynucleotides encoding Factor VIII variants for expression in mammalian cells. In some embodiments, the disclosure also provides mammalian gene therapy vectors and methods for treating hemophilia A. In some embodiments, the present disclosure provides methods for dosing a hemophilia A patient with a polynucleotide, e.g., a codon-altered polynucleotide, encoding a Factor VIII polypeptide.

Provided herein are compositions and methods for treating succinic semialdehyde dehydrogenase deficiency (SSADHD). Compositions may include a gene encoding a functional succinic semialdehyde dehydrogenase (SSADH) enzyme, such as ALDH5A1, operably linked to a targeting vector. The functional SSADII enzyme is envisioned to lower the levels of circulating gamma-hydroxybutyric acid (GHB) and γ-aminobutyric acid (GABA). In some embodiments, combination therapies are envisioned, comprising administering to the subject therapeutically effective amounts of a combination of a composition comprising a gene encoding a functional SSADII enzyme operably linked to a targeting vector; one or more mTOR inhibitors; and a GABA-T inhibitor. Suitable mTOR inhibitors include rapamycin, while suitable GABA-T inhibitors include vigabatrin.

The present invention is directed to genetically-modified non-human animal models with specific mutations in exon 3 of proline-rich acidic protein 1 (PRAP1) gene. Also disclosed herein are methods of treating hyperlipidemia or a hyperlipidemia-related disease by using a PRAP1 inhibitor or a modified PRAP1 polypeptide, as well as pharmaceutical compositions comprising the modified PRAP1 polypeptide.