Ovine adenovirus vectors mediate efficient gene transfer to skeletal muscle

Ovine adenovirus (OAV) vectors represent a promising fool for human gene th erapy since these vectors overcome the problem of pre-existing immunity aga inst human adenovirus vectors. in this report we investigated the in vivo c haracteristics of this novel vector system with respect to its potential fo r gene transfer into skeletal muscle. We found that moderate doses of an OA V-derived vector expressing the human alpha(1)-antitrypsin gene (OAVhaat) i nfected skeletal muscle in mice very efficiently resulting in high serum hA AT levels. The infection was restricted to skeletal muscle, but gene expres sion was transient and vector DNA was rapidly cleared. Vector clearance was also observed with a vector that lacked the transgene. The loss of vector DNA was accompanied by a cellular immune response in the infected muscle bu t was not connected with detectable expression of early or late genes of th e viral backbone as analyzed by RT-PCR. A very low dose of OAVhaat (3 x 10( 7) infectious particles) was sufficient to produce reasonable amounts (> 10 0 ng/ml) of serum hAAT, and this was accompanied by a weak immune response to the vector. Under these conditions, a second intramuscular injection of the same recombinant OAV vector was successful. Our study expands the known tissue tropism of OAV-derived vectors in vivo and points to the possible u tility of the vector for muscle gene transfer and vaccination.