The invention generally provides methods for producing recombinant AAV viral particles using cells grown in suspension. The invention provides recombinant AAV particles for use in methods for delivering genes encoding therapeutic proteins, and methods for using the recombinant AAV particles in gene therapy.

The present invention is directed to HSV-1 vectors which rely on the tetracycline repressor and operator as a means for regulating expression. The vectors utilize VP-16 responsive promoters of HSV to control expression of the tetracycline repressor. The vectors are of particular interest as vehicles for recombinantly expressing genes in vivo.

Methods and compositions relating to the engineering of an improved protein with homocyst(e)inase enzyme activity are described. For example, there are disclosed modified cystathionine-γ-lyase (CGL) enzymes comprising one or more amino acid substitutions and capable of degrading homocyst(e)ine. Furthermore, provided are compositions and methods for the treatment of homocystinuria or hyperhomocysteinemia with homocyst(e)ine depletion using the disclosed enzymes or nucleic acids.

Methods and compositions relating to the engineering of an improved protein with homocyst(e)inase enzyme activity are described. For example, there are disclosed modified cystathionine-γ-lyase (CGL) enzymes comprising one or more amino acid substitutions and capable of degrading homocyst(e)ine. Furthermore, provided are compositions and methods for the treatment of homocystinuria or hyperhomocysteinemia with homocyst(e)ine depletion using the disclosed enzymes or nucleic acids.

The present invention discloses a modified interleukin 12 (nsIL-12) and its gene, recombinant vector and use in manufacture of a medicament for treatment of tumors. When the oncolytic adenovirus vector carrying the modified interleukin 12 gene targets tumor tissue, the modified interleukin 12 is continuously expressed at a low level and mainly distributed in the local tumor tissue, which improves the specificity to tumor cells and reduces the systemic toxicity of interleukin 12; the modified interleukin 12 shows stronger inhibitory effect on tumor growth in intraperitoneally disseminated tumors and orthotopic tumors, and has low toxicity. The modified interleukin 12 armed oncolytic viruses show excellent anti-tumor effects, with a significant regression of tumors and lower toxicity compared with the existing IL-12 armed virus.

The present invention discloses a modified interleukin 12 (nsIL-12) and its gene, recombinant vector and use in manufacture of a medicament for treatment of tumors. When the oncolytic adenovirus vector carrying the modified interleukin 12 gene targets tumor tissue, the modified interleukin 12 is continuously expressed at a low level and mainly distributed in the local tumor tissue, which improves the specificity to tumor cells and reduces the systemic toxicity of interleukin 12; the modified interleukin 12 shows stronger inhibitory effect on tumor growth in intraperitoneally disseminated tumors and orthotopic tumors, and has low toxicity. The modified interleukin 12 armed oncolytic viruses show excellent anti-tumor effects, with a significant regression of tumors and lower toxicity compared with the existing IL-12 armed virus.

The present invention discloses novel recombinant multivalent non-pathogenic Marek's Disease virus constructs that encode and express foreign antigens from three or more avian viruses, along with methods of the use of the multivalent poultry virus vaccines.

A recombinant herpes virus showing high antitumor activity is provided. In particular, a recombinant herpes simplex virus that expresses an ICP6 gene under control of a tumor-specific promoter or tissue-specific promoter on the genome of the virus is provided.

In one embodiment, the invention provides an HSV vector comprising a mutant gB and/or a mutant gH glycoprotein, where the viral envelope further comprises a non-native ligand specific for a protein present on the surface of a predetermined cell type. In another embodiment, the invention provides an HSV vector comprising (a) a mutant gC and/or gD envelope glycoprotein which comprises a non-native ligand specific for a protein present on the surface of a predetermined cell type; and (b) a mutant envelope glycoprotein other than gD.

The present invention provides recombinant herpesvirus of turkeys (HVT) vectors that contain and express antigens of avian pathogens, compositions comprising the recombinant HVT vectors and polyvalent vaccines comprising the recombinant HVT vectors. The present invention further provides methods of vaccination against a variety of avian pathogens and method of producing the recombinant HVT vectors.