Genetic Engineering for CNS Regeneration

Publisher Summary There is a rich array of possible intervention points and times in stimulation of central nervous system (CNS) repair using genetic engineering techniques. These can be broken down into three cell categories: neurons, pathways, and innervation targets—and three time intervals—immediately after injury, during neurite regrowth, upon target recognition, and upon reinnervation. At the time of injury it should be possible to inject vectors and cells directly into the damaged site. The most nontoxic, yet efficient direct gene delivery vectors in the current formulations would be adenovirus and adenoassociated virus (AAV), gutless adenovirus, helper virus-free herpes simplex virus (HSV) amplicons, and lentivirus. Genes that might be helpful for neurons in the injury period include those coding for anti-apoptotic proteins or protective proteins for free radicals. Grafted cells could be preprogrammed genetically with a pro-drug-activation suicide gene, so that systemic application of the pro-drug would lead to cell death. An ideal system would be activation of a cell death geneunder the control of a tetracycline inducible promoter.