The invention provides modified HSV vectors that exhibit enhanced entry of cells, either through direct infection and/or lateral spread. In one aspect, HSV vectors of the present invention can directly infect cells through interaction with cell proteins other than typical mediators of HSV infection. In another aspect, the invention provides an HSV vector, which exhibits lateral spread in cells typically resistant to HSV lateral spread, such as cells lacking gD receptors. The invention further provides DNA encoding mutant forms of the HSV gB and gH glycoproteins, stocks of the inventive virus, and methods for effecting viral targeting and efficient entry of cells. The invention also pertains to the use of the inventive vectors for treating cancers.

Disclosed is a method for administering a transgene into a fibroblast in a subject comprising: a) providing a herpes simplex virus (HSV) comprising a recombinant herpes simplex virus genome, wherein said recombinant herpes simplex virus genome comprises one or more transgenes encoding a polypeptide to be expressed in said fibroblast; and b) providing a pharmaceutically acceptable carrier, wherein said HSV has reduced cytotoxicity as compared to a wild-type herpes simplex virus.

The present disclosure relates to replication-competent controlled herpesviruses whose transient replication in a desired inoculation site region of a subject can be activated by the delivery of an appropriate heat dose to the inoculation site region. In related recombinant viruses, activation requires delivery of a heat dose in the presence in the inoculation site region of an effective concentration of a small-molecule regulator. The viruses are further engineered to be capable of replicating efficiently in the desired inoculation site region but essentially not in nerve ganglia and other nerve cells.

Proposed are a recombinant herpes simplex virus having a modified glycoprotein gH for retargeting and the use thereof. Particularly, the recombinant herpes simplex virus is capable of infecting a target cell having a target molecule to which a cell-targeting domain specifically recognizes and binds due to the presence of the cell-targeting domain in the glycoprotein gH thereof, and is thus useful for anticancer therapy or gene therapy.

The invention provides a method for ameliorating chronic pain signaling involving transient receptor potential cation channel subfamily V member 1 (TRPV1) by expressing PP1 in neurons. The invention also provides HSV vectors for expressing PP1 within neurons and compositions comprising such vectors.

The present invention provides a recombinant oncolytic Herpes Simplex Virus (oHSV) comprising a non-HSV ligand specific for a molecule (protein, lipid, or carbohydrate determinant) present on the surface of a cell (such as a cancer cell) and one or more copies of one or more microRNA target sequences inserted into one or more HSV gene loci, preferably one or more HSV gene(s) required for replication of HSV in normal (i.e., non-cancerous) cells. The invention further provides stocks and pharmaceutical compositions comprising the inventive oHSV and methods for killing tumor cells employing the inventive oHSV.

The invention provides viral vectors (e.g., herpes viral vectors) and methods of using these vectors to treat disease.

Disclosed herein are high transducing replication defective herpes simplex virus (HSV) vectors of McKrae strain.

A composition for expressing a polypeptide within a target organ, the composition comprising a delivery particle, and at least a first mRNA sequence complexed with, encapsulated by, or otherwise associated with the delivery particle. The mRNA sequence comprises a coding sequence which codes for the polypeptide, at least a first untranslated region (UTR) sequence, and at least one micro-RNA (miRNA) binding site sequence, wherein the miRNA binding site sequence is located within, immediately 5 to, or immediately 3 to, the first UTR sequence. The composition may be used in combination with or to supplement other therapeutic approaches, including chemotherapy, oncolytic viral therapy, and cellular therapies. Methods for making and using the composition are provided, particularly in treatment of disease, such as cancer of the liver, brain, lung, breast and pancreas.

An HSV vector with ICP27 under control of CXCR4 promoter and ICP34.5 under control of miRNA-124/143, wherein the vector has a deletion of one RL and one RS region of the viral genome. Within optional embodiments the mutation is a deletion containing the second copy of the ICP34.5 gene. These constructs provide increased safety without sacrificing efficacy. The HSV vector also incorporates a virus-expressed cytokine cassette encoding IL-12, IL-15/IL-15RA under the control of CMV promoter.