A gene delivery method long sought in the field of gene therapy: a deactivated virus carrying a gene of interest that can be injected into the bloodstream and make its way to the right cells, is being developed by researchers at Washington University School of Medicine in St. Louis who are working in mice.
In this early proof-of-concept study, the scientists have shown that they can target tumor blood vessels in mice without affecting healthy tissues.
Advertisement"Most current gene therapies in humans involve taking cells out of the body, modifying them and putting them back in," said David T. Curiel, MD, PhD, distinguished professor of radiation oncology. "This limits gene therapy to conditions affecting tissues like the blood or bone marrow that can be removed, treated and returned to the patient. Today, even after 30 years of research, we can't inject a viral vector to deliver a gene and have it go to the right place."
But now, investigators at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine say they have designed a "targetable injectable vector" - a deactivated virus that homes in on the inner lining of tumor blood vessels and does not get stuck in the liver, a problem that has plagued past attempts.
The findings are reported Dec. 23 in PLOS ONE.
Building on their own previous work and others', the researchers engineered this viral vector to turn on its gene payload only in the abnormal blood vessels that help fuel and nurture tumor growth. But unlike most therapies aimed at tumor vasculature, the goal is not to destroy the cancer's blood supply.
"We don't want to kill tumor vessels," said senior author Jeffrey M. Arbeit, MD, professor of urologic surgery and of cell biology and physiology. "We want to hijack them and turn them into factories for producing molecules that alter the tumor microenvironment so that it no longer nurtures the tumor. This could stop the tumor growth itself or cooperate with standard chemotherapy and radiation to make them more effective. One advantage of this strategy is that it could be applied to nearly all of the most common cancers affecting patients."
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