Adenovirus-mediated prenatal gene transfer to murine central nervous system

In some lysosomal storage disorders pathological alterations in the central nervous system (CNS) occur as early as the prenatal period and the neuropathology progresses rapidly soon after birth. In these diseases, postnatal therapies alone are often insufficient. Therefore prenatal gene therapy to the CNS may be necessary. In order to investigate the feasibility of gene transfer to the CNS prenatally, we administered recombinant adenovirus carrying LacZ gene to rat embryos from embryonic day 9 to 12 (E9-E12). Results showed that efficient transduction of the reporter gene to the CNS was achieved when adenoviruses were injected at E12. The regions where the reporter gene was transduced mainly localized at the telencephalon and hypophysis of the embryo, and the gene expression persisted at least 1 week after birth. In addition, when adenoviruses were injected at E9, E10 and E11, no transgene expression was detected in the CNS, but was mainly observed in the liver, the heart and the skin, respectively.