Provided herein are methods and compositions useful in the production of recombinant AAV (rAAV) in host producer cells, such as insect cells. In some embodiments, methods, uses and compositions are provided that comprise recombinant VP1 genes comprising modified Kozak sequences to express AAV VP1 proteins in amounts that are useful for producing infective rAAV particles. These infective rAAV particles may comprise a gene of interest.

Provided herein are methods and compositions useful in the production of recombinant AAV (rAAV) in host producer cells, such as insect cells. In some embodiments, methods, uses and compositions are provided that comprise recombinant VP1 genes comprising modified Kozak sequences to express AAV VP1 proteins in amounts that are useful for producing infective rAAV particles. These infective rAAV particles may comprise a gene of interest.

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.

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.

In order to improve the efficiency of gene introduction in CAR therapy employing a transposon method, provided is a method for preparing genetically-modified T cells expressing chimeric antigen receptor, comprising: (1) a step of preparing non-proliferative cells which are obtained by stimulating a group of cells comprising T cells using an anti-CD3 antibody and an anti-CD28 antibody followed by a treatment for causing the cells to lose their proliferation capability; (2) a step of obtaining genetically-modified T cells into which a target antigen-specific chimeric antigen receptor gene has been introduced using a transposon method; (3) a step of mixing the non-proliferative cells prepared by step (1) with the genetically-modified T cells obtained by step (2), and co-culturing the mixed cells while stimulating the mixed cells using an anti-CD3 antibody and anti-CD28 antibody; and (4) a step of collecting the cells after culture.

In order to improve the efficiency of gene introduction in CAR therapy employing a transposon method, provided is a method for preparing genetically-modified T cells expressing chimeric antigen receptor, comprising: (1) a step of preparing non-proliferative cells which are obtained by stimulating a group of cells comprising T cells using an anti-CD3 antibody and an anti-CD28 antibody followed by a treatment for causing the cells to lose their proliferation capability; (2) a step of obtaining genetically-modified T cells into which a target antigen-specific chimeric antigen receptor gene has been introduced using a transposon method; (3) a step of mixing the non-proliferative cells prepared by step (1) with the genetically-modified T cells obtained by step (2), and co-culturing the mixed cells while stimulating the mixed cells using an anti-CD3 antibody and anti-CD28 antibody; and (4) a step of collecting the cells after culture.

The present invention relates to treatment of AR-related disorders by modulating the levels of AR2, which is a naturally occurring AR variant and is capable of modulating AR transcriptional activity.

The present invention relates to treatment of AR-related disorders by modulating the levels of AR2, which is a naturally occurring AR variant and is capable of modulating AR transcriptional activity.

The present disclosure provides variant adeno-associated virus (AAV) capsid polypeptides that provide an AAV particle with the ability to traverse the human blood brain barrier (BBB) and transduce cells of the CNS. In some embodiment, a subject variant AAV capsid protein includes an amino acid sequence having 95% or more sequence identity (e.g., 96% or more, 97% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity) with the amino acid sequence set forth in any one of SEQ ID NOs: 1-27. Also provided are nucleic acids, AAV vectors, viral particles, cells, kits, and methods.

The present disclosure provides variant adeno-associated virus (AAV) capsid polypeptides that provide an AAV particle with the ability to traverse the human blood brain barrier (BBB) and transduce cells of the CNS. In some embodiment, a subject variant AAV capsid protein includes an amino acid sequence having 95% or more sequence identity (e.g., 96% or more, 97% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity) with the amino acid sequence set forth in any one of SEQ ID NOs: 1-27. Also provided are nucleic acids, AAV vectors, viral particles, cells, kits, and methods.