Synthetic, persistent RNA vectors for controlled expression of one or more heterologous polynucleotide sequences, each of the one or more heterologous polynucleotide sequences encoding for a reprogramming factor, are described. The vectors comprise a mechanism for silencing (off) and initiation or resumption (on) control of expression of the one or more reprogramming factors in the cell, tissue, or organ. Methods of using the vectors are also described, for example, to treat the age-related disease or condition, where the methods provide for treatment of the disease or condition, and in some embodiments, with retention of cellular identity.

The invention provides compositions and methods for treating diseases associated with expression of a tumor antigen as described herein. The invention also relates to nucleic acids comprising a truncated PGK promoter operably linked to a chimeric antigen receptor (CAR) specific to a tumor antigen as described herein, vectors encoding the same, and recombinant T cells comprising the CARs of the present invention. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises an antigen binding domain that binds to a tumor antigen as described herein.

This invention provides RNA, oligoribonucleotide, and polyribonucleotide molecules comprising pseudouridine or a modified nucleoside, gene therapy vectors comprising same, methods of synthesizing same, and methods for gene replacement, gene therapy, gene transcription silencing, and the delivery of therapeutic proteins to tissue in vivo, comprising the molecules. The present invention also provides methods of reducing the immunogenicity of RNA, oligoribonucleotide, and polyribonucleotide molecules.

This invention provides RNA, oligoribonucleotide, and polyribonucleotide molecules comprising pseudouridine or a modified nucleoside, gene therapy vectors comprising same, methods of synthesizing same, and methods for gene replacement, gene therapy, gene transcription silencing, and the delivery of therapeutic proteins to tissue in vivo, comprising the molecules. The present invention also provides methods of reducing the immunogenicity of RNA, oligoribonucleotide, and polyribonucleotide molecules.

The present invention concerns methods and compositions for gene therapy, in particular in vivo gene therapy for delivery of bioactive glial derived neurotrophic factor (GDNF) for the treatment of Parkinson's Disease. The invention also concerns mammalian cells capable of producing GDNF in increased amounts as well as the use of these cells for recombinant production of bioactive GDNF and for therapeutic use. The invention also includes a device that may be implanted in the cochlear of a patient that is capable of secreting GDNF.

The present invention concerns methods and compositions for gene therapy, in particular in vivo gene therapy for delivery of bioactive glial derived neurotrophic factor (GDNF) for the treatment of Parkinson's Disease. The invention also concerns mammalian cells capable of producing GDNF in increased amounts as well as the use of these cells for recombinant production of bioactive GDNF and for therapeutic use. The invention also includes a device that may be implanted in the cochlear of a patient that is capable of secreting GDNF.

The invention provides an isolated and purified nucleic acid sequence encoding a chimeric antigen receptor (CAR) directed against B-cell Maturation Antigen (BCMA). The invention also provides host cells, such as T-cells or natural killer (NK) cells, expressing the CAR and methods for destroying multiple myeloma cells.

A red blood cell extracellular vesicle (RBCEV) loaded with a nucleic acid cargo; method for preparing the loaded vesicle; and the therapeutic use of the vesicle thereof are disclosed. The nucleic acid cargoes may be DNA or RNA, single stranded or double stranded, as well as linear or circular.

An isolated recombinant soluble endothelial cell protein C receptor (r-sEPCR) for use as a hemostatic agent.

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.