The present invention provides a retroviral or lentiviral vector having a viral envelope which comprises a mitogenic T-cell activating transmembrane protein which comprises: (i) a mitogenic domain which binds a mitogenic tetraspanin, and (ii) a transmembrane domain; wherein the mitogenic T-cell activating transmembrane protein is not part of a viral envelope glycoprotein. When cells such as T-cells or Natural Killer cells are transduced by such a viral vector, they are activated by the mitogenic T-cell activating transmembrane protein.

Disclosed herein are compositions of retroviruses and methods of using the same for gene delivery to a hematopoietic stem cell (HSC), wherein the retroviruses comprise a viral envelope protein comprising at least one mutation that diminishes its native function, a non-viral membrane-bound protein comprising a membrane-bound domain and an extracellular targeting domain.

Methods and compositions are provided for delivery of a polynucleotide encoding a gene of interest, typically an antigen, to a dendritic cell (DC). The virus envelope comprises a DC-SIGN specific targeting molecule. The methods and related compositions can be used to treat patients suffering from a wide range of conditions, including infection, such as HIV/AIDS, and various types of cancers.

Compositions comprising a polymeric micellar nanoparticle composition comprising a block or graft copolymer comprising at least one polycationic polymer and at least one polyethylene glycol (PEG) polymer having an average molecular weight less than 1 kDa, and at least one nucleic acid, wherein the graft or block copolymer and at least one nucleic acid are complexed and condensed into a shaped micellar nanoparticle that is stable in biological media are disclosed. The presently disclosed subject matter also provides a method for preparing the presently disclosed polymeric micellar nanoparticle compositions, a method for targeting at least one metastatic cancer cell in a subject, and a method for treating a disease or condition using the presently disclosed polymeric micellar nanoparticle compositions.

The present invention relates to a recombinant self-assembled protein comprising a target-oriented peptide and a use thereof. The recombinant self-assembled protein according to the present invention, comprising a target-oriented peptide, does not require an additional process for providing target-orientedness, and is thus capable of delivering a desired drug to a target tissue or target cell without using additives, such as chemical binders or stabilizers; therefore, the protein can be used for photothermal therapy, drug delivery, imaging, or the like. In particular, according to the present invention, it is possible to prepare gold-protein nanoparticle fusions in which uniform high-density gold nanoparticles having target-orientedness are bound to protein surfaces, without an additional process of surface stabilization or process for providing target-orientedness. Compared with conventional gold nanoparticles, the gold-protein nanoparticle fusions according to the present invention show structural stability against pH variation and concentration variation, and also have excellent target-orientedness; therefore, the fusions can bring a dramatic enhancement to the utilization of gold nanoparticles in photothermal therapy.

The present invention describes compositions and methods for priming protective immunity in the presence of pre-existing maternal antibody. In some embodiments, the invention contemplates simultaneously masking vaccines to avoid antibody neutralization while targeting those vaccines to specific cell types in order to elicit an enhanced immune response. In other embodiments, vectors that recruit and activate specific antigen-presenting cells may further enhance the efficacy of those immune responses.

Amyloid precursor protein (APP) dysfunction is a key feature in Alzheimer's disease (AD). The sortilin-related receptor 1 (SORLA) functions as a chaperone protein to APP and has reduced expression in AD brains. The APP and SORLA dysfunction results in homeostasis destabilization. Herpesviruses are suspected to be involved in AD pathogenesis. Using a strategic nucleotide BLAST to query SORL1 and APP nucleotide alignment on all Herpesviridae genomes identified similarity sequences from the Epstein-Barr virus and herpes simplex virus 2. The invention describes a treatment to alleviate EBV and HSV2-mediated neurodegeneration by delivering antisense oligonucleotides sequences that target the EBV and HSV2 non-coding sequences to block SORLA and APP disruption. The invention further describes methods to eradicate EBV infection by delivering inducible expression of antisense oligonucleotides targeting EBV genes or an inducible CRISPR/Cas gene-editing system, together with an expression construct encoding anti-apoptotic proteins or with anti-apoptotic proteins for the prevention of cell-mediated apoptosis.

Described is a targeting construct encoding a modified Sindbis virus envelope protein, comprising mutations in the E1, E2 and/or E3 proteins, fused with a monomeric biotin-binding molecule. Lentiviral vectors pseudotyped with the novel envelope proteins, such as E2 71 eMA and E2 71 mSAH, can be conjugated with biotinylated targeting ligands The conjugated ligands mediate specific binding and transduction of the target cell types. This lentiviral transduction system can be used to selectively deliver transgenes into specific cell types in vivo, which increases the numbers of vectors reaching the targeted cells and tissues and decreases adverse effects in non-targeted cells and tissues. The vectors transduce B cells without conjugation of targeting ligands. The B cell type most efficiently transduced in this manner is long-lived plasma cells, and thus can be used for long-term transgene expression.

The present invention provides a retroviral or lentiviral vector having a viral envelope which comprises: (i) a mitogenic T-cell activating transmembrane protein which comprises a mitogenic domain and a transmembrane domain; and/or (ii) a cytokine-based T-cell activating transmembrane protein which comprises a cytokine domain and a transmembrane domain, wherein the mitogenic or cytokine-based T-cell activating transmembrane protein is not part of a viral envelope glycoprotein. When cells such as T-cells of Natural Killer cells are transduced by such a viral vector, they are simultaneously activated by the mitogenic T-cell activating transmembrane protein and/or the cytokine-based T-cell activating transmembrane protein.

The present invention provides a retroviral or lentiviral vector having a viral envelope which comprises: (i) a mitogenic T-cell activating transmembrane protein which comprises a mitogenic domain and a transmembrane domain; and/or (ii) a cytokine-based T-cell activating transmembrane protein which comprises a cytokine domain and a transmembrane domain, wherein the mitogenic or cytokine-based T-cell activating transmembrane protein is not part of a viral envelope glycoprotein. When cells such as T-cells of Natural Killer cells are transduced by such a viral vector, they are simultaneously activated by the mitogenic T-cell activating transmembrane protein and/or the cytokine-based T-cell activating transmembrane protein.