ADENOVIRAL VECTOR AS A GENE DELIVERY SYSTEM INTO CULTURED RAT NEURONAL AND GLIAL-CELLS

Previous studies have demonstrated that a defective recombinant adenov irus can infect a wide range of postmitotic and slowly proliferating c ell types such as hepatocytes, myotubes, pneumocytes and intestinal ce lls (Stratford-Perricaudet et al., Hum. Gene Ther., 1, 241 - 256, 1990 ; Quantin et al., Proc. Natl. Acad. Sci. USA, 89, 2581 - 2584, 1992; J affe et al., Nature Genetics, 1, 372 - 378, 1992). We have used a defe ctive recombinant adenovirus, Ad.RSVbetagal, containing the Escherichi a coli beta-galactosidase gene targeted to the nucleus under the trans criptional control of the Rous sarcoma virus long terminal repeat prom oter (Stratford-Perricaudet et al., J. Clin. Invest., 90, 626 - 630, 1 992) to infect non-dividing neural cells in primary culture. We show t hat 80 - 1 00% of neuronal and astroglial cells infected with a viral titre lower than 10(9) p.f.u./ml express beta-galactosidase for at lea st 1 month without cell damage. These results demonstrate the potentia l usefulness of recombinant adenovirus infection for the analysis of b rain-specific gene regulation and for the transfer of genes into neura l cells before their transplantation into the brain.