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 present disclosure relates to a viral gene delivery vector particle and a bispecific polypeptide configured to bind a viral gene delivery vector particle and target cell-specific receptor protein. The disclosure also relates to gene delivery systems, compositions, and methods of use thereof.

Provided are polynucleotides and viral vectors, particularly, alphavirus vectors such as Sindbis viral vectors, which encode multiple, e.g., two or more, epitopes of at least one tumor associated antigen in which each epitope is separated by a processing or enzyme cleavage site. The multiple epitopes of the two or more tumor associated antigens encoded by the described polynucleotides and viral vectors may be the same or different. Methods of treating mammalian subjects having a cancer or tumor expressing the tumor associated antigen epitopes are provided, in which the viral vectors encoding the multiple epitopes, as well as other immunostimulatory or immunomodulatory components, generate an anti-cancer or anti-tumor immune response in which high levels of effector T cells increase the survivability of tumored mammalian subjects and result in epitope spreading, thus providing a further enhancement of the immune response.

The present invention refers to a composition comprising a viral protein or fragment thereof, wherein the viral protein or fragment thereof is enclosed within a self-assembling protein nanocapsule, preferably ferritin, and wherein the viral protein, or fragment thereof is selected from a virus of the Togaviridae family. The viral protein or fragment thereof may also further be selected from a virus of the alphavirus subfamily.

Aspects of the disclosure relate to nucleic acid vaccines. The vaccines include one or more RNA polynucleotides having an open reading frame encoding one or more Chikungunya antigen(s), one or more Zika virus antigens, and one or more Dengue antigens. Methods for preparing and using such vaccines are also described.

The present disclosure provides a system for the expression of target protein in conjunction with enhancer protein. The enhancer protein may be a viral protein that blocks nucleocytoplasmic transport. Also provided are polynucleotides, vectors, and cells comprising target protein and enhancer protein nucleic acid sequences.

Disclosed herein are self-replicating RNA molecules encoding prostate neoantigens, vaccines, and methods of treating and preventing prostate cancer.

Synthetic alphavirus-derived replicon expression systems comprising nucleic acid sequences encoding at least one modified nonstructural protein, and synthetic nucleic acid sequences encoding at least one heterologous protein are described. Methods of producing at least one heterologous protein in a cell, or of inducing an immune response in a subject by administering and/or expressing the synthetic alphavirus-derived replicon expression systems are provided.

The present invention relates to high-titer hybrid vims vectors which produce virus-like vesicle (VLVs) and compositions and methods thereof for targeting a malignancy or infectious disease. VLVs are a capsid-free, self-replicating artificial virus platform carrying positive-strand capped and polyadenylated RNA encoding an in vitro evolved Semliki Forest vims (SFV) RNA-dependent RNA replicase and the vesicular stomatitis virus (VSV) glycoprotein. The VLVs of the present invention and pharmaceutical compositions thereof encode for polynucleotide and/or polypeptide therapeutic agents useful in methods for the treatment, prophylaxis, and prevention of malignancies and infectious diseases.

Provided herein are pseudotyped recombinant lyssavirus particles and methods for their use in delivering a transgene into a target cell. Also provided are packaging systems and methods of using the packaging systems to produce pseudotyped recombinant lyssavirus particles.