In vivo gene transfer in mouse skeletal muscle mediated by baculovirus vectors

Baculovirus vectors are efficient tools for gene transfer into mammalian ce lls in vitro. However, in vitro gene delivery by systemic administration is hindered by the vector inactivation mediated by the complement system. To characterize further the gene transfer efficacy of baculovirus we examined the vector transduction efficiency in skeletal muscle. Vectors expressing v esicular stomatitis virus glycoprotein (VSV-G) in the viral envelope were g enerated by inserting the VSV-G coding sequence downstream of the polyhedri n promoter. Two viruses were constructed to carry either the Escherichia co li beta -galactosidase (beta -Gal) gene or the mouse erythropoietin (EPO) c DNA cloned downstream of the cytomegalovirus immediate-early promoter and e nhancer, The greater gene transduction efficiency of the Bac-G-beta Gal vec tor was confirmed by comparing the betaP-Gal expression level in a variety of human and mouse cell lines with that obtained on infection with Bac-beta Gal, a vector that lacks VSV-G. Similarly, a 5- to 10-fold increase in bet a -Gal expression between Bac-G-beta Gal and Bac-beta Gal was observed when mouse myoblasts and myotubes were infected. The same increase in beta -Gal expression was detected on injection of the Bac-G-beta Gal vector in the q uadriceps of BALB/c and C57BL/6 mice. In contrast, a 2-fold difference in t ransduction was observed between these two vectors in DBA/2J mouse strain. Last, expression of EPO cDNA was detected for at least 178 days in DBA/2J m ice on Bac-G-EPO injection into the quadriceps whereas EPO expression decli ned to normal values by 35 days postinfection in BALB/c and C57BL/6 mice. T hus, these results indicate that baculovirus may be considered a useful vec tor for gene transfer in mouse skeletal muscle and that persistence of expr ession may depend on the mouse strain used.