Provided are compositions, systems, and methods useful for effecting gene editing in eukaryotic cells. Compositions include plasmids that encode one or more viral fusion proteins in which one or more viral proteins are fused with an aptamer-binding protein. Compositions also include plasmids that encode a non-viral nucleic acid sequence, wherein the non-viral nucleic acid sequence encodes a CRISPR system component. In some instances, the non-viral nucleic acid sequence also includes an aptamer sequence. The plasmids can be used to generate viral particles, including lentivirus-like particles that contain a viral fusion protein and a non-viral RNA sequence. Systems of producing such viral particles are provided. Also provided are methods of using the viral particles of the disclosure to effect gene editing in eukaryotic cells.

The present invention provides polypeptides for selectively inducing target antigen-specific CD8-positive T-cell responses. Since induction of human immunodeficiency virus (HIV)-specific CD4-positive T-cell responses by vaccine could promote HIV infection, an HIV vaccine antigen that selectively induces HIV-specific CD8-positive T-cell responses would be useful if obtained. Thus, in the present invention, polypeptide antigens were designed in which 8- to 12-residue amino acid sequences divided from the amino acid sequence of a target antigen protein were connected in an order different from that of the original amino acid sequence. DNA and viral vector vaccines expressing these antigens were tested by inoculation into monkeys. As a result, they were shown to be able to efficiently induce antigen-specific CD8-positive T-cell responses in a selective manner. The instant antigens may be useful as vaccine antigens that induce CD8-positive T cells in a highly selective manner.

The present disclosure provides fusion proteins that incorporate unique mechanisms for multimerizing antigens to enhance their immunogenicity. The fusion proteins comprise at least two antigens, or other vaccine related proteins, separated by a linker sequence and an oligomerization domain. When expressed, the fusion protein forms a muKimeric protein complex, This approach can be used to muHimeri?.e a single antigen/protein or to create multimers comprising two or more different antigens/proteins. Also provided are nucleic acids encoding the fusion proteins. Yet another aspect is directed to methods of inducing or suppressing an immune response in a subject by administering to the subject a vaccine composition comprising a fusion protein or nucleic acid encoding the fusion protein, optionally without using an adjuvant.

This disclosure relates to recombinant bacteria, e.g. L. lactis, expressing heterologous pili containing human immunodeficiency virus (HIV) antigens. In certain embodiments, the recombinant bacteria are administered in combination with other HIV antigens, nucleic acids encoding HIV antigens, recombinant virus encoding HIV antigens, anti-viral agents and/or adjuvants in an effective amount to elicit a mucosal immune response against HIV.

Provided here are certain recombinant HIV compositions and animal models to evaluate prophylactic and therapeutic antiviral compositions.

A lentiviral vector system for expressing a lentiviral particle is disclosed. The lentiviral vector system includes a therapeutic vector. The therapeutic vector comprises a phenylalanine hydroxylase (PAH) sequence for expressing at least one of PAH or a variant thereof, wherein the PAH sequence is truncated.

Increased viral particle maturation and production can be achieved in various methods for producing viral particles from viral proteins, in general, by inhibiting or preventing Heme Oxygenase 2 (HO-2) from binding to the group-specific antigen (Gag) of the viral proteins, thus allowing delivery of the viral proteins to plasma membranes where they can replicate and mature without interference from HO-2. The increase in viral particle maturation and production can also be achieved by minimizing or eliminating the presence of HO-2 to thus reduce or prevent binding of HO-2 to the group-specific antigen (Gag) of the viral proteins. The invention is particularly applicable to the production of lentiviruses from viral proteins wherein the Matrix domain (MA) of the Gag is myristoylated.

Provided are a lentivirus packaging vector and a packaging method thereof. The lentivirus packaging vector contains a first LTR, a reversely inserted gene expression cassette and a second LTR, wherein the first LTR is positioned upstream of the reversely inserted gene expression cassette in the direction of viral genome expression; the second LTR is positioned downstream of the reversely inserted gene expression cassette in the direction of viral genome expression; the gene expression cassette contains a promoter, a repressible operon, a gene of interest and a polyadenylation signal, which are connected in sequence; and in the presence of a repressor, the repressible operon represses the expression of the gene of interest.

The present invention relates to retroviral vectors, particularly lentiviral vectors, comprising a modified retroviral RNA sequence that is codon-substituted and comprises a reduced number of retroviral open-reading frames, and wherein the retroviral vector is pseudotyped with hemagglutinin-neuraminidase (HN) and fusion (F) proteins from a respiratory paramyxovirus, methods of making the same and uses thereof.

Disclosed are the optimal composition and size of DNA/polycation particles for efficient transfection of viral production cells in both adherent and suspension cultures. The size-dependent feature of DNA/polycation particle-mediated transfection for particles between 50 nm and 1000 nm also is disclosed. A new scalable method based on kinetic control of DNA/polycation nanoparticle assembly to prepare shelf-stable particles with defined sizes between 50 nm and 1000 nm also is disclosed. The presently disclosed DNA/polycation particles yield superior and reproducible transfection activity and shelf stability and can be used as an off-the-shelf product.