An oncolytic virus with improved safety and anticancer effects and uses thereof are disclosed. The oncolytic virus contains a recombinant nucleic acid including a nucleotide sequence encoding an effector domain derived from herpes simplex virus thymidine kinase (HSV-TK). The oncolytic virus can express an HSV-TK fragment which contains an effector domain composed of a minimum amino acid sequence capable of phosphorylating GCV or ACV while having no thymidine kinase (TK) activity, or a variant thereof to phosphorylate GCV or ACV, thereby killing cancer cells infected with the oncolytic virus and even neighboring cancer cells.

Nucleic acid sequences encoding improved Herpes Simplex Virus Thymidine Kinases are provided, including their use in diagnostic and therapeutic applications. The thymidine kinases may be mutated using conservative mutations, non-conservative mutations, or both. Also provided are gene therapeutic systems, including viral and retroviral particles.

The modified HSV gD protein of the present invention is a modified protein of a herpes simplex virus (HSV) envelope glycoprotein D (gD), wherein the modified HSV gD protein is derived from a wild-type HSV gD by modification of at least one of B cell epitopes having low or no neutralizing antibody-inducing activity compared to a B cell epitope present in a receptor-binding domain (RBD) (decotopes) in the ectodomain of the wild-type HSV gD, so that the modified epitope does not function as an epitope.

Disclosed herein are polypeptides for use in treating diseases associated with pathogenic genomic repeat sequences, such as neurological disorders. Also disclosed are nucleic acid molecules and vectors that encode such polypeptides. Therapeutic uses and methods for treating such diseases are also disclosed; in particular, therapeutic uses and methods comprising complementary pairs and combinations of therapeutic polypeptides, nucleic acids or vectors. Also disclosed is a method and associated peptides and nucleic acids for active, long-term delivery of therapeutic molecules to target cells in vivo or in vitro.

Provided herein are compositions and methods for vaccination and research applications. In particular, provided herein are non-neuroinvasive herpesviruses and alpha herpesviruses and uses thereof.

The disclosure provides a non-natural herpes simplex virus (“HSV”), compositions comprising, or alternatively consisting essentially of, or yet further consisting of the HSV, and methods of producing the HSV, or infecting a cell with the HSV. Also provided herein are methods of treating cancer or inhibiting the growth or metastasis of cancer cell in a subject in need thereof.

The invention relates to stabilised pre-fusion conformation Class III fusion proteins. The inve ntion also provides vaccine compositions for immunising a subject against viral infections.

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 provides vaccines for treating or preventing a herpes simplex virus infection and methods of using and making the vaccine. Further provided are recombinant herpes simplex virus genomes, recombinant viruses, and immunogenic compositions.

The present invention is directed to a recombinant herpesvirus comprising a heterologous polypeptide ligand capable of binding to a target molecule and fused to or inserted into glycoprotein B at specific sites. The herpesvirus may comprise more than one ligand, and the additional ligand(s) may be comprised by a modified glycoprotein D and/or modified glycoprotein H. This allows the herpesvirus to 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 gB, a polypeptide comprising the gB, 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.