APPLICATION OF RECOMBINANT ADENOVIRUS FOR IN-VIVO GENE DELIVERY TO SPINAL-CORD

One strategy for treating spinal cord injury is to supply damaged neur ons with the appropriate neurotrophins either by direct delivery or by transfer of the corresponding genes using viral vectors. Here we repo rt the feasibility of using recombinant adenovirus for in vivo gene tr ansfer in spinal cord. After injection of a recombinant adenovirus car rying a beta-galactosidase (beta-gal) reporter gene into the mid-thora cic spinal cord of adult rats, transgene expression occurred not only in several types of cells around the injection site but also in neuron s whose axons project to this region from rostral or caudal to the inj ection site. Among labeled neurons were those of the red nucleus, the vestibular nuclei, reticular formation, locus coeruleus, and Clarke's nucleus. A non-specific immune reaction, which could be blocked by imm unosuppression with Cyclosporin A, reduced the number of transduced ce lls surviving at the injection site by 1 month. In neurons away from t he injection site, where the immune response was minimal, transgene ex pression lasted for at least 2 months. These results support the idea that recombinant adenovirus can be used in the spinal cord for in vivo delivery of therapeutic genes important for supporting neuron surviva l and axon regeneration. (C) 1997 Elsevier Science B.V.