Provided herein are regulatable expression systems and methods of using said regulatable expression systems to express proteins of interest. The regulatable expression systems comprise a unidirectional regulatable promoter operably linked to a single transcription unit encoding a protein of interest, a ribosome skip, and a transactivator protein.

Disclosed are a composition and method of treating or preventing cardiomyopathy in a human subject. In one embodiment, a method comprises delivering a gene therapy drug to cardiac tissue of the human subject. The gene therapy drug comprises: a first vector comprising a first portion of a polynucleotide sequence encoding for a therapeutic protein; and a second vector comprising a second portion of the polynucleotide sequence encoding for the therapeutic protein.

Disclosed are a composition and method of treating or preventing cardiomyopathy in a human subject. In one embodiment, a method comprises delivering a gene therapy drug to cardiac tissue of the human subject. The gene therapy drug comprises: a first vector comprising a first portion of a polynucleotide sequence encoding for a therapeutic protein; and a second vector comprising a second portion of the polynucleotide sequence encoding for the therapeutic protein.

Disclosed herein are recombinant AAV variant (e.g., variant serotype 3B (AAV3B)) capsid proteins and variant capsid protein-containing viral particles with enhanced ability to transduce hepatic cells. Viral particles containing these capsid variants are capable of evading neutralization by the host humoral immune response. The recombinant AAV3B variant proteins and viral particles disclosed herein were identified from a variant AAV3B capsid library that was engineered by making substitutions in only the variable regions of the capsid. Some embodiments of the AAV3B capsid variants disclosed herein comprise the AAV3B-G3 variant and the AAV3B-E12 variant. Compositions of these variant AAV particles are provided that are useful for transducing and delivering therapeutic transgenes to cells, such as liver cells, and thus treat diseases and disorders pertaining to these cells.

Disclosed herein are recombinant AAV variant (e.g., variant serotype 3B (AAV3B)) capsid proteins and variant capsid protein-containing viral particles with enhanced ability to transduce hepatic cells. Viral particles containing these capsid variants are capable of evading neutralization by the host humoral immune response. The recombinant AAV3B variant proteins and viral particles disclosed herein were identified from a variant AAV3B capsid library that was engineered by making substitutions in only the variable regions of the capsid. Some embodiments of the AAV3B capsid variants disclosed herein comprise the AAV3B-G3 variant and the AAV3B-E12 variant. Compositions of these variant AAV particles are provided that are useful for transducing and delivering therapeutic transgenes to cells, such as liver cells, and thus treat diseases and disorders pertaining to these cells.

Disclosed herein are compositions that include antigen-encoding nucleic acid sequences and/or antigen peptides. Also disclosed are nucleotides, cells, and methods associated with the compositions including their use as vaccines, including vectors and methods for a heterologous prime/boost vaccination strategy.

Regulatory T cells (T.sub.reg cells), formerly known as suppressor T cells, are crucial for the maintenance of immunological tolerance. Their major role is to shut down T cell-mediated immunity toward the end of an immune reaction and to suppress auto-reactive T cells that escaped the process of negative selection in the thymus. Two major classes of CD4.sup.+ T.sub.reg cells have been described—naturally occurring T.sub.reg cells and adaptive T.sub.reg cells. Disclosed herein are methods for producing efficacious CAR T.sub.reg cells in a GMP-scalable system.

Regulatory T cells (T.sub.reg cells), formerly known as suppressor T cells, are crucial for the maintenance of immunological tolerance. Their major role is to shut down T cell-mediated immunity toward the end of an immune reaction and to suppress auto-reactive T cells that escaped the process of negative selection in the thymus. Two major classes of CD4.sup.+ T.sub.reg cells have been described—naturally occurring T.sub.reg cells and adaptive T.sub.reg cells. Disclosed herein are methods for producing efficacious CAR T.sub.reg cells in a GMP-scalable system.

Methods for Producing Populations of High Titer Recombinant Adeno-Associated Virus (rAAV) Lacking Prokaryotic Sequences are disclosed.

Methods for Producing Populations of High Titer Recombinant Adeno-Associated Virus (rAAV) Lacking Prokaryotic Sequences are disclosed.