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November 2, 2016

Artificial Cancer-Killing Virus the Longest Yet Synthesized

  • It is the genome of an oncolytic virus, it is 34,000 base pairs long, and it is 100% artificial. It’s important because it not only has immediate application in studies of canine cancer, it also promises to inform the development of human therapies. In these human therapies, artificial viruses could be customized to such an extent, that they could qualify as personalized anticancer therapeutics.

    The virus in question in sCAV2, a conditionally replicative adenovirus (CRAd) that can target and kill tumor cells while sparing healthy cells. It was synthesized by scientists affiliated with Gen9, who worked in concert with scientists representing Autodesk and Auburn University. At Auburn, scientists led by Bruce Smith, V.M.D., Ph.D., intend to use the synthetic virus to evaluate therapeutic treatments in dogs with osteosarcoma, a type of bone cancer with a survival rate of less than 10%.

    According to a press release issued November 2 by the principals, the synthesis of the sCAV2 virus was accomplished by means of Gen9’s BioFab DNA synthesis platform, which Gen9 describes as an industrialized chip-based technology for gene synthesis. Gen9 asserts that its platform can produce mass quantities of high-quality long-length clonal DNA constructs at prices as low as 3 cents per base pair.

    When used to synthesize the sCAV2 virus, the Gen9 platform reduced the timeframe for development from months to weeks, enabling Dr. Smith and his team to drastically accelerate their research.

    “The technology to create a new virus by synthesizing it is a huge leap, but the ability to then make a customized virus tailored to the specific needs of each patient will be transformative,” said Dr. Smith. “This could change the way we fight cancer. It is that revolutionary.”

    The potential to develop knowledge about oncolytic viruses in canines, and then to apply this knowledge to humans was of keen interest even before synthetic genomes became so practical. For example, a recent review (MacNeil, Oncolytic Virother. 2015; 4: 95–107) noted that oncolytic viral therapy is a promising treatment option that may prove to be relatively inexpensive and effective against several types of cancer.

    “The efficacy of oncolytic virus therapies has been clearly demonstrated in murine cancer models, but the positive outcomes observed in mice are not always seen in human cancer patients,” the review indicated. “These therapies should be thoroughly evaluated in dogs with spontaneously arising cancers to provide needed information about the potential effectiveness of virus treatment for human cancers and to promote the health of our companion animals.”

    Studies of oncolytic virus therapies may soon explore previously unattainable depths, now that the synthesis of viral genomes has demonstrated such power. “The construction of this viral genome is a tremendous step for DNA synthesis and its application to therapeutics research,” said Devin Leake, Ph.D., vice president of research and development at Gen9.

    “At Autodesk, we’ve been prototyping the ‘3D printing’ of medicines for several years,” added Andrew Hessel, distinguished research scientist in the Autodesk BioNano Research Group, and the catalyst behind the project. “This work demonstrates that personalized, made-on-demand therapies are within reach, and our efforts in combatting cancer in dogs could lead the way in next-generation care.”

    The potential for personalizing viruses for use against cancer may spur interest in oncolytic virus studies. Such interest, argued the review article cited above, has already reached the popular media. “A report by the HBO series Vice focused on trials using recombinant poxvirus, measles virus, and lentivirus to treat a variety of cancers,” the review noted. “The CBS news show 60 Minutes aired interviews with researchers and patients involved in trials using a modified poliovirus to treat patients with glioblastoma.”

    The review speculated that this type of press could help direct additional funding to studies of oncolytic viruses. If so, attracting funding could become even easier now that therapeutic oncolytics have shown promise as a form of personalized medicine.

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