The present disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding a polypeptide; viruses comprising the recombinant nucleic acids; compositions comprising the recombinant nucleic acids and/or viruses; methods of their use; and articles of manufacture or kits thereof.

The present disclosure provides recombinant adeno-associated virus (rAAV) virions with an engineered capsid protein. In particular, the disclosure provides AAV9 virions with engineered AAV9 capsid, AAV5/9 chimeric capsid or combinatory capsid that achieves increased transduction efficiency in cardiac cells, increased cell-type selectivity, and/or other desirable properties.

Disclosed herein are compositions and in vitro and in vivo methods for reprogramming post-natal (adult and juvenile) tissue into insulinogenic cells. These compositions and methods are useful for a variety of purposes, including the development of diabetes therapies.

Provided herein are methods that include introducing into an inner ear of a mammal a therapeutically effective amount of an adeno-associated virus (AAV) vector that includes a nucleotide sequence encoding (a) a polypeptide including an antibody heavy chain variable domain operably linked to a signal peptide and a polypeptide including an antibody light chain variable domain operably linked to a signal peptide; (b) a polypeptide including an antigen-binding antibody fragment operably linked to a signal peptide; or (c) a soluble vascular endothelial growth factor receptor operably linked to a signal peptide.

Methods of editing target nucleic acids are provided using a guide RNA and a Cas9 protein to excise exons in a target gene and where the edited gene is expressed to produce a truncated polypeptide.

NK cells and NK cell lines are modified so as to have a more cytotoxic phenotype, namely to have reduced function of Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1). Methods of making the modified cells and cell lines, compositions comprising the modified cells and cell lines, as well as uses of said cells, cell lines and compositions in therapy are also provided.

Provided are an AAV capsid protein mutant and an encoding nucleic acid, and a corresponding vector and a host cell thereof. Also provided are an adeno-associated virus vector containing the AAV capsid protein mutant, a recombinant adeno-associated virus particle constructed therefrom and carrying a gene expression cassette, a preparation method therefor, and the use thereof in treating diseases.

Phosphatidylinositol 3-kinases (PI3Ks) are known to be important regulators of signaling pathways. To determine whether PI3Ks are genetically altered in cancers, we analyzed the sequences of the PI3K gene family and discovered that one family member, PIK3CA, is frequently mutated in cancers of the colon and other organs. The majority of mutations clustered near two positions within the PI3K helical or kinase domains. PIK3CA represents one of the most highly mutated oncogenes yet identified in human cancers and is useful as a diagnostic and therapeutic target.

The disclosure provides gene therapy vectors, such as adeno-associated virus (AAV), designed for treatment of an immunoglobulin- .Math. binding protein 2 (IGHMB P2)-related disorder.

A pharmaceutical composition formulated for delivery of a recombinant adeno-associated virus (rAAV) vector comprising an AAV capsid and a vector genome having human galactosylceramidase (GALC) coding sequence is provided. Also provided are 5 methods and uses of a pharmaceutical composition comprising a rAAV for the treatment of Krabbe disease.