The present invention relates to an oncolytic virus which is, or is derived from, a clinical isolate which has been selected by comparing the abilities of a panel of three or more clinical isolates of the same viral species to kill tumor cells of two or more tumor cell lines in vitro and selecting a clinical isolate which is capable of killing cells of two or more tumor cell lines more rapidly and/or at a lower dose in vitro than one or more of the other clinical isolates in the panel.

Provided herein are non-naturally occurring variants of the hepatitis B virus (HBV) Core protein, the HBV polymerase N-terminal domain, and the HBV polymerase C-terminal domain, as well as immunogenic fragments thereof. Fusion proteins comprising the HBV variants fused to a herpes simplex virus (HSV) glycoprotein (gD) sequence, as well as methods of using the fusion proteins, are also provided.

The present disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding an immunomodulatory polypeptide (e.g., a pro-inflammatory cytokine such as a human IL-2 or IL-12 polypeptide); viruses comprising the recombinant nucleic acids; compositions and formulations comprising the recombinant nucleic acids and/or viruses; methods of their use (e.g., for the treatment of cancer, such as lung cancer); and articles of manufacture or kits thereof.

The present invention is directed to a recombinant herpesvirus comprising a heterologous peptide and optionally polypeptide ligand capable of binding to (a) target molecule(s) and fused to or inserted into glycoprotein D. The recombinant herpesvirus may additionally comprise modifications for detargeting the virus from the natural receptors of gD. This allows the herpesvirus to efficiently target a cell for therapeutic purposes and a cell for virus production. The present invention further comprises a pharmaceutical composition comprising the herpesvirus, the herpesvirus for use in the treatment of a tumor, infection, degenerative disorder or senescence-associated disease, a nucleic acid and a vector coding for the gD, a polypeptide comprising the gD, and a cell comprising the herpesvirus, nucleic acid, vector or polypeptide. Moreover, a method for infecting a cell with the herpesvirus or for producing the herpesvirus is disclosed.

A combined artificial cell death/reporter system polypeptide containing a herpes simplex virus thymidine kinase (HSV-tk) fused to a prostate-specific membrane antigen (PSMA) polypeptide via a linker is described. Also described are polynucleotides encoding the artificial cell death polypeptide, cells expressing the artificial cell death polypeptide and related methods.

The present disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding a Serine Protease Inhibitor Kazal-type (SPINK) polypeptide (e.g., a SPINK5 polypeptide); viruses comprising the recombinant nucleic acids; compositions and formulations comprising the recombinant nucleic acids and/or viruses; methods of their use (e.g., for the treatment of Netherton Syndrome); and articles of manufacture or kits thereof.

The present invention relates to an oncolytic virus comprising: (i) a fusogenic protein-encoding gene; and (ii) an immune stimulatory molecule-encoding gene.

Methods of vaccinating, immunizing and/or treating a subject against a herpes simplex virus infection or a disease caused by a herpes simplex virus infection comprise administering to the subject an effective amount of a HSV-2 single-cycle virus and an effective amount of a recombinant HSV-2 glycoprotein D, wherein the HSV-2 single-cycle virus comprises HSV-2 having a deletion of glycoprotein D-encoding gene in the genome and the HSV-2 is phenotypically complemented with an HSV-1 glycoprotein D on a lipid bilayer of the HSV-2.

Adeno-associated virus (AAV) Clade F vectors or AAV vector variants (relative to AAV9) for precise editing of the genome of a cell and methods and kits thereof are provided. Targeted genome editing using the AAV Clade F vectors or AAV vector variants provided herein occurred at frequencies that were shown to be 1,000 to 100,000 fold more efficient than has previously been reported. Also provided are methods of treating a disease or disorder in a subject by editing the genome of a cell of the subject via transducing the cell with an AAV Clade F vector or AAV vector variant as described herein and further transplanting the transduced cell into the subject to treat the disease or disorder of the subject. Also provided herein are methods of treating a disease or disorder in a subject by in vivo genome editing by directly administering the AAV Clade F vector or AAV vector variant as described herein to the subject.

The invention relates to the field of virology and tumor therapy. In particular, the present invention provides a recombinant herpes simplex virus (HSV) capable of specifically replicating at a high level in a tumor cell and effectively killing the tumor cell, but replicating at low levels in normal cells, thereby the recombinant herpes simplex virus of the present invention not only has high lethality against tumor cells, but also has significantly decreased side effects (especially neurotoxicity). Further, the present invention relates to a viral vector constructed based on the recombinant herpes simplex virus, a pharmaceutical composition comprising the recombinant herpes simplex virus or the viral vector, and the use of the recombinant herpes simplex virus or the viral vector. The recombinant herpes simplex virus of the present invention can be used to infect and kill tumor cells, and can be used for gene drug delivery into tumor cells for gene therapy.