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 invention is directed to Herpes simplex-2 viruses that may be used in vaccines to immunize patients against genital herpes.

A chimeric oncolytic virus is described that includes a herpesvirus having a modified nucleic acid sequence, including a modification of the herpesvirus gamma (1)34.5 gene (γ.sub.134.5) or a nucleic acid with at least about 70% homology to the γ.sub.134.5 gene that reduces its expression; a second viral nucleic acid sequence encoding a PKR evasion protein that does not cause virulence; and a third nucleic acid sequence encoding a tumor-associated antigen. Methods of using the chimeric oncolytic virus to treat subjects having cancer, or to vaccinate subjects at risk of developing cancer, are also described.

Methods for passive transfer of immunity using recombinant herpes simplex virus 2 (HSV-2) vaccine vectors, virions thereof, compositions and vaccines comprising such.

A malaria vaccine composition is disclosed herein that uses liver-stage parasite exported proteins as the target of a protective immune response instead of sporozoite proteins. Also disclosed is a recombinant viral particle that comprises a fusion protein disclosed herein, wherein the malaria antigen is displayed within the viral particle. Also disclosed is an isolated polynucleotide that comprises a nucleic acid sequence encoding a fusion protein disclosed herein operably linked to an expression control sequence. Also disclosed is a recombinant herpes simplex virus (HSV) genome comprising a modified VP26 gene encoding a fusion protein disclosed herein. Also disclosed is a vaccine composition that comprises a recombinant viral particle disclosed herein in a pharmaceutically acceptable excipient. In some cases, the composition further comprises an adjuvant.

The present disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding a cystic fibrosis transmembrane conductance regulator (CFTR) polypeptide (e.g., a human CFTR 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 a chronic lung disease, such as cystic fibrosis); and articles of manufacture or kits thereof.

The present invention relates to oncolytic virus comprising: (i) a GM-CSF-encoding gene; and (ii) an immune co-stimulatory pathway activating molecule or an immune co-stimulatory pathway activating molecule-encoding gene.

Recombinant herpes simplex virus (HSV)-1 capable of selectively replicating in alternative lengthening of telomeres (ALT)-dependent tumor cells are described. The recombinant HSV-1 are ICP0-deficient, such as by complete deletion of the ICP0 gene, or mutation of the ICP0 gene sufficient to diminish or eliminate E3 ubiquitin ligase activity of ICP0. In some cases, the recombinant HSV-1 further include additional gene deletions or mutations, such as those that render the virus glycoprotein C (gC) deficient, or include a heterologous gene, such as a gene encoding an immunostimulatory molecule. Methods of treating ALT-dependent cancer, and methods of selectively killing ALT-dependent tumor cells are also described.

The invention provides improved compositions and methods for the treatment of solid cancers.

This invention relates generally to a codon optimized nucleic acid encoding a retinitis pigmentosa GTPase regulator (RPGR) protein. The nucleic acid has enhanced stability during plasmid production relative to a wildtype cDNA encoding the RPGR protein. The invention also relates to expression cassettes, vectors, and host cells comprising the codon optimized nucleic acid. Methods for preparing a recombinant adeno-associated (rAAV) expression vector comprising the codon optimized nucleic acid sequence are also provided. The nucleic acids, expression cassettes, vectors, and host cells provided may be useful in the large scale production of rAAV expression vectors for gene therapy applications.