Adenoviral Vector as a Gene Delivery System into Cultured Rat Neuronal and Glial Cells

Abstract

Previous studies have demonstrated that a defective recombinant adenovirus can infect a wide range of postmitotic and slowly proliferating cell types such as hepatocytes, myotubes, pneumocytes and intestinal cells (Stratford-Perricaudet et al., Hum. Gene Ther., 1, 241–256, 1990; Quantin et al., Proc. Natl. Acad. Sci. USA, 89, 2581–2584, 1992; Jaffe et al., Nature Genetics, 1, 372–378, 1992). We have used a defective recombinant adenovirus, Ad.RSVβgal, containing the Escherichia coliβ-galactosidase gene targeted to the nucleus under the transcriptional control of the Rous sarcoma virus long terminal repeat promoter (Stratford-Perricaudet et al., J. Clin. Invest., 90, 626–630, 1992) to infect non-dividing neural cells in primary culture. We show that 80–100% of neuronal and astroglial cells infected with a viral titre lower than 10⁹ p.f.u./ml express β-galactosidase for at least 1 month without cell damage. These results demonstrate the potential usefulness of recombinant adenovirus infection for the analysis of brain-specific gene regulation and for the transfer of genes into neural cells before their transplantation into the brain.