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2001 FEB 8 - (NewsRx.com) -- by Michelle Marble, staff medical writer -- New technique incorporates recombinant adenovirus (rAd) and adeno-associated virus (AAV) vectors for in utero gene therapy, researchers in the United States reported.
"We have developed a micro-injection technique to deliver recombinant adenovirus and AAV to mouse fetuses at day 15 after conception," wrote M. Mitchell and colleagues, Children's National Medical Center, Washington, DC ("Long-term gene transfer to mouse fetuses with recombinant adenovirus and adeno-associated virus (AAV) vectors," Gene Therapy, 2000;7(23):1986-1992).
"Several routes of delivery, including injections to the amniotic fluid, the front limb, the placenta, the liver, and the retro-orbital venus plexus, were tested using an El-deleted recombinant adenovirus (Ad.CBlacZ) or a recombinant adeno-associated virus (AAV.CMV1acZ) carrying a beta-galactosidase (lacZ) gene," continued the researchers.
They reported that Ad.CBlacZ injection into the amniotic cavity resulted in transgene expression in the skin and in the digestive tract of the fetuses. Ad.CBlacZ injection in the front limb resulted in LacZ expression in all major muscle groups around the injection site as well as low levels of expression in the liver. The other three routes of delivery - intraplacental, intra-hepatic, and retro-orbital injections of Ad.CBlacZ - all led to lacZ expression predominantly in the liver.
"Further studies revealed a maximal tolerant dose (defined as the highest viral dose with [less than or equal to] 20% mortality in the injected fetuses) of ...