Triggering neuronogenesis by endogenous brain stem cells with DNA nanoplexes

An understanding of the mechanisms that control the transition of neural stem/progenitor cells (NS/PC) into functional neurons could potentially be used to recruit endogenously produced NS/PCs for neuronal replacement in a variety of neurological diseases. The elucidation and therapeutic control of neuronogenic mechanisms requires the ability to manipulate gene expression in NS/PCs in vivo. Nanotechnology has provided new therapeutic tools such as non-viral vectors for DNA delivery. We have employed organically modified silica-DNA nanoplexes capable of forming complexes with plasmid DNA for effective in vivo transfection of NS/PC in the mouse subventricular zone (SVZ). Using DNA nanoplexes for transfection, neuronogenesis can be effectively stimulated by genes engineered to target the integrative nuclear FGF receptor-1 signaling (INFS) pathway, a novel developmental mechanism that enhances the latent potential of NS/PCs to undergo neuronal differentiation. This novel nanobiological technology may open a new horizon for the treatment of a broad range of neurological disorders.