Targeting serotype 3 receptor enhances gene transfer efficiency.(Brief Article)

2002 APR 18 - (NewsRx.com & NewsRx.net) -- by Sonia Nichols, senior medical writer - Investigators at the University of Alabama may have found a way to overcome at least one of the problems associated with unsatisfactory transfer efficiency in ovarian cancer patients treated with gene therapy.

"Gene delivery efficiency in clinical cancer gene therapy trials with recombinant adenoviruses (Ads) based on serotype 5 (Ad5) has been limited partly because of variable expression of the primary Ad5 receptor, the coxsackie and adenovirus receptor (CAR), on human primary cancer cells," noted Anna Kanerva and coauthors, University of Alabama, Birmingham in Clinical Cancer Research.

Investigative efforts made by the research team have lead to the development of a new way to target gene therapy to cancer cells, most specifically ovarian cancer cells, by using newly devised viral constructs containing structural elements from alternative Ad serotypes.

"We have constructed an Ad5-based vector, Ad5/3luc1, with a chimeric fiber protein featuring a knob domain derived from Ad3," Kanerva and associates said. Because the recombined viral vector contains an affinity for Ad3 receptors, researchers can redirect the types of tissue it targets in cancer gene therapy.

This became evident when, after treating several ovarian cancer cell lines with Ad5/luc or Ad5/3luc1 using three different levels of viral titer, Kanerva and coauthors were able to confirm that Ad5/3luc1 was ...