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Fiber modification enables viral vectors to skirt receptor deficiency.
2002 JUN 20 - (NewsRx.com & NewsRx.net) -- by Sonia Nichols, senior medical writer - Medical investigators have discovered that fiber modification enables adenoviral vectors to transfer genes to ovarian cancer cells effectively despite variable expression of cellular receptors.
Previous studies have shown the coxsackie-adenovirus receptor (CAR) is important for successful gene transfer when adenovirus serotype 5 (Ad5) viruses are used for gene delivery. However, researchers have determined that CAR expression can be variable on cancer cells. Now though, a team at the University of Alabama at Birmingham in the Division of Human Gene Therapy have devised viral modifications of adenoviruses (Ad) that thwart inadequate CAR expression.
"Ad5/3luc1 incorporates the serotype 3 fiber knob and binds to a receptor distinct from CAR, while the fiber of Ad5lucRGD is modified with an RGD-4C motif, allowing CAR-independent binding to integrins," A. Kanerva and colleagues said about the modified adenoviruses.
Researchers administered intravenous and intraperitoneal injections of the viruses to mice implanted with tumors, checking the animals for clearance as well as biodistribution following inoculation. They also analyzed gene transfer efficacy using murine ovarian cancer models as well as ovarian cancer cell lines.
"Ad5/3luc1 achieved improved gene transfer over Ad5lucRGD, and both infectivity-enhanced viruses were superior to the isogenic control with an ...
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Source: HighBeam Research, Fiber modification enables viral vectors to skirt receptor deficiency.