A modified adenovirus capable of overcoming the problem of low level of coxsackie-adenovirus receptor (CAR) expression on tumor cells and methods of using such adenovirus are provided. The fiber protein of the adenovirus is modified by insertion or replacement so as to target the adenovirus to tumor cells, and the replication of the modified adenovirus is limited to tumor cells due to specific promoter control or mutations in E1a or E1b genes.

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.

Described herein are virus-like particles (VLPs) and minimal human-derived virus-like particles (mhVLPs), comprising a membrane comprising a phospholipid bilayer with one or more human-derived envelope glycoproteins (env) on the external side. Optionally, a biomolecule cargo is disposed in the core of the VLP or mhVLP on the inside of the membrane. Preferably, the mhVLPs do not comprise any exogenous virally derived proteins, e.g., proteins from viral gag, pro, or pol, or other viral proteins that reside inside of enveloped particles (unless the cargo comprises the viral protein(s)). In some embodiments, the mhVLPs do not comprise any human endogenous retroviral (HERV) proteins other than the env (hENV), e.g., do not comprise gag, pol, or pro that was exogenously introduced into producer cells. In some embodiments, the VLPs include a targeting domain, either fused at the N or C terminus or internally into the hENV, or as a separate membrane-anchored targeting domain. Also described are methods of use of the VLPs or mhVLPs for delivery of the biomolecule cargo to cells.

The present invention relates to a recombinant virus of the family Paramyxoviridae, comprising at least one expressible polynucleotide encoding a multispecific binding polypeptide, said multispecific binding polypeptide comprising a first binding domain binding to a surface molecule of an immune cell with antitumor activity, preferably a lymphocyte, more preferably a T cell or a dendritic cell, and a second binding domain binding to a tumor-associated antigen; to a polynucleotide encoding the same, and to a kit comprising the same. Moreover, the present invention relates to a method for treating cancer in a subject afflicted with cancer, comprising contacting said subject with a recombinant virus of the family Paramyxoviridae of the invention, and thereby, treating cancer in a subject afflicted with cancer.

Disclosed herein are compositions of retroviruses and methods of using the same for gene delivery, 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.

The invention provides novel methods, materials and systems that can be used to generate viral vectors having altered tissue and cell targeting abilities. In illustrative embodiments of the invention, the specificity of lentiviral vectors was modulated by a thin polymer shell that synthesized and coupled to the viral envelope in situ. The polymer shell can confers such vectors with new targeting ability via agents such as cyclic RGD (cRGD) peptides that are coupled to the polymer shell. These polymer encapsulated viral vectors exhibit a number of highly desirable characteristics including a higher thermal stability, resistance to serum inactivation in vivo, and an ability to infect dividing and non-dividing cells with high efficiencies.

The invention provides novel methods, materials and systems that can be used to generate viral vectors having altered tissue and cell targeting abilities. In illustrative embodiments of the invention, the specificity of lentiviral vectors was modulated by a thin polymer shell that synthesized and coupled to the viral envelope in situ. The polymer shell can confers such vectors with new targeting ability via agents such as cyclic RGD (cRGD) peptides that are coupled to the polymer shell. These polymer encapsulated viral vectors exhibit a number of highly desirable characteristics including a higher thermal stability, resistance to serum inactivation in vivo, and an ability to infect dividing and non-dividing cells with high efficiencies.

The present invention relates to a recombinant virus of the family Paramyxoviridae, comprising at least one expressible polynucleotide encoding a multispecific binding polypeptide, said multispecific binding polypeptide comprising a first binding domain binding to a surface molecule of an immune cell with antitumor activity, preferably a lymphocyte, more preferably a T cell or a dendritic cell, and a second binding domain binding to a tumor-associated antigen; to a polynucleotide encoding the same, and to a kit comprising the same. Moreover, the present invention relates to a method for treating cancer in a subject afflicted with cancer, comprising contacting said subject with a recombinant virus of the family Paramyxoviridae of the invention, and thereby, treating cancer in a subject afflicted with cancer.

A method of targeting bacterially-derived, intact minicells to specific, non-phagocytic mammalian cells employs bispecific ligands to deliver nucleic acids efficiently to the mammalian cells. Bispecific ligands, comprising (i) a first arm that carries specificity for a bacterially-derived minicell surface structure and (ii) a second arm that carries specificity for a non-phagocytic mammalian cell surface receptor are useful for targeting minicells to specific, non-phagocytic mammalian cells and causing endocytosis of minicells by non-phagocytic cells.

Compositions of retroviruses and methods of using the same for gene delivery, 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.