CULTURED HUMAN MYOBLASTS AND MYOTUBES SHOW MARKEDLY DIFFERENT TRANSDUCIBILITY BY REPLICATION-DETECTIVE ADENOVIRUS RECOMBINANTS

Human adenovirus (AV) is a favored vector for delivery oi therapeutic genes into certain target cells, such as skeletal muscle cells for gen e therapy. Here we show that replication-defective (E(1) + E(3) delete d) human type 5 adenovirus (AV) recombinants reporter gene insert (RSV -luciferase or RSV-Lux) can very efficiently transduce cultured human myoblasts. However, transduction efficiency is about one order of magn itude less in cultured myotubes 16 days postfusion. The high transduct ion of myoblasts by AV-RSV-Lux could be effectively blocked by an argi nine-glycine-asparagine (RGD) oligopeptide that serves as a ligand for the natural internal,ization receptor of AV. The normalized level of beta(3)/beta(5)-integrin, the main component of the 1 internalization receptor for AV is about three times as abundant in myoblasts than in myotubes. This could contribute, among other things, to the relatively high 1 susceptibility of myoblasts to AV infection and AV-mediated ge ne transduction.