Cationic lipids and polymers are able to enhance adenoviral infection of cultured mouse myotubes

Adenovirus-mediated gene transfer has been used to promote efficient expres sion of various reporter and therapeutic transgenes such as minidystrophin in skeletal muscle tissue. However, down-regulation of the adenovirus inter nalisation receptors, alpha(v)beta(3) and alpha(v)beta(5), in adult myofibr es and in mature cultured myotubes makes them less susceptible to infection than neonatal muscle or cultured myoblasts. It has been reported elsewhere that adenoviral transduction of cells that are normally refractory to infe ction can be enhanced by complexing virus particles with cationic lipids or cationic polymers. In this study we describe increased levels of adenoviru s-mediated transduction of cultured C2C12 myotubes, when the vector is comp lexed with either of the cationic lipids Lipofectamine or 1,3-dioleoyloxy-2 -(6-carboxyspermyl)propylamide (DOSPER) or the cationic polymer polyethylen imine. The presence of polycations allowed a smaller dose of adenovirus vec tor to be used to attain the same level of infection seen with adenovirus a lone, which has important relevance-to future in vivo studies, Electron mic roscopic analysis of adenovirus/polycation complexes showed large aggregate s as opposed to single adenovirus particles in the absence of polycations. Finally, by complexing adenovirus particles with polycations, partial prote ction against the neutralising effect of adenovirus antiserum was observed.