Sustained effects of gene-activated matrices after CNS injury

We show that when gene-activated matrices (GAM) are placed between the prox imal and distal stumps of severed rat optic nerves, DNA is retained within the GAM, promoting sustained transgene expression in the optic nerve, in th e GAM itself, and, more importantly, in axotomized retinal ganglion cells ( ROC), Plasmids that encode basic fibroblast growth factor (FGF2), brain-der ived neurotrophic factor (BDNF), and neurotrophin-3 (NT3) promote sustained survival of RGC for over 3 months after the initial injury. These findings suggest that immobilized DNA implanted into a CNS lesion will be delivered by axon terminal uptake and retrograde transport to axotomized neurons. GA M may therefore be a useful agent for promoting sustained neuron survival a nd axon regeneration. Whether further optimization of the matrices, plasmid s, promoters, and genes present in the GAM will promote even more survival or, alternatively, axon regeneration remains to be determined.