Vaccinia virus (VACV or VV) is a large, complex, enveloped virus which belongs to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 kbp in length, and which encodes approximately 250 genes. VACV is the active constituent of the vaccine that eradicates smallpox, making it the first human disease to be eradicated. Vaccinia virus can also be engineered as oncolytic virus by mutation of Thymidine Kinase (TK) and Vaccinia Growth Factor (VGF) to attenuate the pathogenicity and increase tumor-specific replication. Nowadays as a tool for delivering genes into cancer cells, the vaccinia virus shows promising clinical efficacy not only in medicine laboratory but also in Phase I and Phase II trials. For years of experience in immunology and oncology, Creative Biolabs has established a comprehensive platform called OncoVirapy™ for providing oncolytic virus development service. By virtue of OncoVirapy™, we are able to design, engineer and generate the most efficacious oncolytic vaccinia viral products.
Different from other DNA viruses, the Vaccinia virus is unique, which replicates only in the cytoplasm of the host cell, outside of the nucleus. Therefore, the large genome is required for encoding various enzymes and proteins involved in viral DNA replication and gene transcription. Due to the large size of its genome, VACV is particularly attractive as a potential antitumor agent. The VACV not only can be engineered as oncolytic virus by mutation of F4L gene encoding the virus homolog of the cell‐cycle‐regulated small subunit of ribonucleotide reductase (RRM2), J2R encoding thymidine kinase (TK), A56R encoding hemagglutinin and Vaccinia Growth Factor (VGF) to attenuate the pathogenicity and increase tumor-specific replication, but also can be armed with foreign genes encoding tumor suppressor protein, immunostimulatory protein, and cytokine, as well as particular enzyme, and even RNAi has been inserted into the nonessential location of VACV genome to treat cancer. Rationally designed combinations of arming gene and oncolytic vaccinia virus may, therefore, be used to produce improved anticancer effects without targeting of the natural cells.
In Creative Biolabs, our brilliant scientists can manipulate and provide various armed oncolytic vaccinia virus for our customer to meet the needs for research, preclinical study and drug development. By pathogenic and immunogenicity manipulation, the virus can specific replicated in the target tumor cells without severe immune reactions. To achieve this, several genes like J2R and A56R are deleted. Advanced modification for increasing viral tropism can be achieved by antisense microRNA (miRT) insertion. The miRT includes but is not limited to miR-122T which is specific to hepatocellular carcinoma (HCC) cells, miR-182T which is specific to uveal melanoma (UM) cells. Arming the immune checkpoint antibody/immune modulation (PD-L1, CTAL-4) or the cytokine/chemokine (IL-12, GM-SCF) can enhance the toxicity of our viral products. Inserting siRNA and shRNA (siNotch1, shVEGF) can increase viral polyfunctionality as well. We also provide customized oncolytic vaccinia virus and proof-of-concept validation study for the oncolytic virus. The OncoVirapy™ platform in the Creative Biolabs provides a one-stop solution to oncolytic virus engineering. Please don’t hesitate to contact us for more information and quotation.
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