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.

The present disclosure provides, among other things, a recombinant adeno-associated viral (rAAV) vector encoding an agent that inhibits the proteolytic activity of plasma kallikrein. The disclosure also provides, a recombinant adeno-associated viral (rAAV) vector encoding an anti/plasma kallikrein antibody heavy drain and an anti-plasma kallikrein antibody light chain.

The subject matter described herein relates to compositions and methods for cellular rejuvenation, tissue engineering, and regenerative medicine by transient exposure of cells or tissues to synthetic, non-integrative mRNAs encoding reprogramming factors. Reprogramming factor encoding polynucleotides and corresponding polypeptides that trigger less immune response, are more stable, and/or exhibit altered activity than wild-type reprogramming factors are provided. RNA vectors expressing one or more of the improved reprogramming factor polynucleotide sequences are also provided.

The present disclosure provides methods and compositions for genetically modifying lymphocytes, for example T cells and/or NK cells. In some embodiments, the methods include reaction mixtures, and resulting cell formulations, that are created using whole blood, or a component thereof that is not a PBMC, and additionally comprise T cells and recombinant retroviral particles having polynucleotides that encode a CAR. In some embodiments, modified lymphocytes are reintroduced into a subject subcutaneously. In some embodiments, polynucleotides that provide T cells the ability to regulate cell survival and proliferation in response to binding to a CAR, are provided.

This invention relates to the use of an adenovirus to treat cancer, for example. The adenovirus may be replication deficient in cells that lack Y box binding protein. The adenovirus may encode an oncogene or an oncogene product, which may transactivate at least one viral gene.

This invention relates to the field of therapeutics. Most specifically, the invention provides methods of generating conditionally expressing vectors for one or more immuunomodulators under the control of a gene expression modulation system in the presence of activating ligand and uses for therapeutic purposes in animals. These vector may be provided to treat a variety of disorders, e.g., neoplastic disorders, through direct injection or through in vitro engineered cells, such as dendritic cells.

The present invention relates to a nucleic acid sequence comprising a nucleotide of interest and a tryptophan RNA-binding attenuation protein (TRAP) binding site, and optionally a Kozak sequence, wherein said TRAP binding site overlaps the Kozak sequence and/or the ATG start codon of the nucleotide of interest. The present invention further relates to a nucleic acid sequence comprising a nucleotide of interest and a Kozak sequence, wherein said Kozak sequence comprises a portion of a tryptophan RNA-binding attenuation protein (TRAP) binding site. The present invention further relates to a nucleic acid sequence comprising a nucleotide of interest and TRAP binding site wherein the TRAP binding site comprises a portion of the start codon ATG of said nucleotide of interest or wherein the ATG start codon comprises a portion of the TRAP binding site. The present invention further relates to a nucleic acid sequence comprising a nucleotide of interest, a binding site for tryptophan RNA-binding attenuation protein (TRAP), a multiple cloning site and a Kozak sequence, wherein said multiple cloning site is overlapping with or located downstream to the 3′ KAGN2-3 repeat of the TRAP binding site and upstream of the Kozak sequence.

The disclosure relates to methods and materials for treating cancer. For example, recombinant vaccinia viruses having the ability to direct the expression of membrane-bound IL-12 polypeptides on the surface of infected cells and methods for using such recombinant vaccinia viruses to treat cancer are provided. Specifically, the disclosure provides a recombinant vaccinia virus comprising a vaccinia virus genome comprising a nucleic acid encoding an IL-12p35 polypeptide sequence and an IL-12p40 polypeptide sequence, wherein one of the polypeptide sequences comprises a membrane anchoring polypeptide sequence.

The disclosure provides gene therapy vectors, such as adeno-associated virus (AAV), optimized for delivering a transgene to muscles. The optimized vectors contain constitutive or a muscle-specific promoter to deliver whole body or skeletal/heart muscle-specific transgene expression, respectively, in combination with a transgene cDNA to replace the gene mutation found in a muscle disease with a normal copy of the gene, an internal ribosomal entry site (IRES) to allow for production of a second protein from the same transcript, and a muscle growth factor, to build new muscle growth and strength. For example, the invention provides The disclosure provides gene therapy vectors, such as recombinant adeno-associated vims (rAAV), designed for treatment of GNE myopathy in which the rAAV expresses UDP-GlcNAc-epimerase/ManNAc-6 alone or in combination with a muscle growth factor or muscle transdifferentation factor. The provided AAV replace the mutated GNE gene expression while expressing proteins that stimulate muscle growth.

The presently disclosed subject matter provides for methods and compositions for treating a neoplasia (e.g., multiple myeloma). It relates to chimeric antigen receptors (CARs) that specifically target Fc Receptor-like 5 (FcRL5), e.g., domain 9 of FcRL5, and immunoresponsive cells comprising such CARs. The presently disclosed FcRL5-targeted CARs have enhanced immune-activating properties, including anti-tumor activity.