The present disclosure provides mammalian cell lines for expression of viral vectors, and methods of making and using the same. Provided methods employ use of identifiers that are capable of being packaged into a viral vector to select and/or identify mammalian cell lines with engineered sequences associated with beneficial characteristics for viral vectors production. Exemplary viral vectors include AAV vectors.

Provided herein are compositions, methods, kits and systems for treating cells, tissues and subjects to alter age-related biology (e.g., to study or to treat age-related diseases and conditions). In particular, provided herein are compositions, methods, and uses for inhibition or modification of sialic acid or its cognate receptor to restore phagocytosis in aged cells.

In one embodiment, the invention provides a herpes simplex virus (HSV) vector that does not express toxic HSV genes in non-complementing cells and which comprises a genome comprising one or more transgenes, wherein the vector is capable of expression of a transgene for at least 28 days in non-complementing cells. The invention also relates to viral stocks of the inventive vectors, compositions thereof suitable for use therapeutically or for in vitro applications, and methods relating thereto. In another aspect, the invention provides a complementing cell engineered to express ICP4 and ICP27 when the cell is infected with HSV for the production of the inventive vector.

A non-integrating viral delivery system is disclosed. The system includes a viral carrier, wherein the viral carrier contains a defective integrase gene; a heterologous viral episomal origin of replication; a sequence encoding at least one initiator protein specific for the heterologous viral episomal origin of replication, wherein expression of the sequence encoding the at least one initiator protein specific for the heterologous viral episomal origin of DNA replication is inducible; and at least one gene, gene product, shRNA, siRNA, miRNA, or other RNA of interest.

A non-integrating viral delivery system is disclosed. The system includes a viral carrier, wherein the viral carrier contains a defective integrase gene; a heterologous viral episomal origin of replication; a sequence encoding at least one initiator protein specific for the heterologous viral episomal origin of replication, wherein expression of the sequence encoding the at least one initiator protein specific for the heterologous viral episomal origin of DNA replication is inducible; and at least one gene, gene product, shRNA, siRNA, miRNA, or other RNA of interest.

A non-integrating viral delivery system is disclosed. The system includes a viral carrier, wherein the viral carrier contains a defective integrase gene; a heterologous viral episomal origin of replication; a sequence encoding at least one initiator protein specific for the heterologous viral episomal origin of replication, wherein expression of the sequence encoding the at least one initiator protein specific for the heterologous viral episomal origin of DNA replication is inducible; and at least one gene, gene product, shRNA, siRNA, miRNA, or other RNA of interest.

The present invention provides highly efficient methods, and compositions related thereto, for generating high titer human antibodies or antibody fragments thereof in a mammalian subject. The methods comprise administering a virus or virus-like particle to a mammal comprising heterologous immune cells and isolating a population of immunoglobulin-producing cells from the mammal, thereby producing the antibodies or antibody fragments thereof.

The invention provides a herpes simplex virus (HSV) vector that does not express toxic HSV genes in non-complementing cells and which comprises a genome comprising one or more transgenes, wherein the vector is capable of expression of a transgene for at least 28 days in non-complementing cells. The disclosed vectors include vectors having deletions in the genes ICP0, ICP4, TCP22, TCP27 and TCP47, or alternative inactivating mutations, or vectors which express one or more of these genes with modified kinetics. The invention also relates to viral stocks of the inventive vectors, compositions thereof suitable for use therapeutically or for in vitro applications, and methods relating thereto. In another aspect, the invention provides a complementing cell, in particular a U20S cell, engineered to express ICP4 and ICP27 when the cell is infected with HSV for the production of the inventive vector. Said cells are disclosed as naturally complementing ICP0.

The present invention relates generally to non-integrating viral delivery system and methods of using the same. The viral delivery systems includes a viral carrier, a heterologous viral episomal origin of replication, a sequence encoding at least one initiator protein specific for the heterologous viral episomal origin of replication, and at least one gene, shRNA, siRNA, miRNA, or other gene-silencing RNA of interest. In certain embodiments, the disclosed system can be used for gene therapy.

The present invention provides highly efficient methods, and compositions related thereto, for generating high titer human antibodies or antibody fragments thereof in a mammalian subject. The methods comprise administering a virus or virus-like particle to a mammal comprising heterologous immune cells and isolating a population of immunoglobulin-producing cells from the mammal, thereby producing the antibodies or antibody fragments thereof.