Effective Gene Transfer into Regenerating Sciatic Nerves by Adenoviral Vectors: Potentials for Gene Therapy of Peripheral Nerve Injury

Department of Biology, Kyunghee University, Seoul, Korea.
Molecules and Cells (Impact Factor: 2.09). 11/2000; 10(5):540-5. DOI: 10.1007/s10059-000-0540-4
Source: PubMed


Replication defective adenoviral vectors have been demonstrated as an effective method for delivering genes into a variety of cell types and tissues both in vivo and in vitro. Transfecting genes into neuronal cells has proven to be difficult because of their lack of cell division. Since the major problem in neurological disease is the degeneration of the terminally differentiated neuronal cells, the adenoviral vector's ability to transfer genes into differentiated post-mitotic cells makes them advantageous for a gene delivery system for the nervous system. Here we showed that a replication defective recombinant adenovirus carrying the lacZ gene could infect the neuronal stem cells and even the differentiated neuronal cells derived from the central nervous system. The lacZ gene delivered into the neuronal cells was expressed efficiently. In addition, the recombinant virus also infected Schwann cells in intact and injured nerves in vivo. The expression of the lacZ gene lasted for 5 weeks, within which nerve regeneration is accomplished in the rat. Adenoviral vectors might thus be used to modulate Schwann cell gene expression for treating peripheral nerve injury or peripheral neuropathy.

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    • "During Wallerian degeneration, a process of gradual nerve degeneration in the distal stump of the injury site when the peripheral nervous system (PNS) is injured, axons and myelin sheaths are degenerated and removed for regrowing axons. When axons outgrow from the nerve ending sites toward the distal stump at the site of injury, Schwann cells remyelinate the new axons [14, 15]. Enhancing the axonal regrowth by any small compounds, it can be therapeutic for improving PNS nerve regeneration. "
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    • "After 2 h, viruses were washed off and cells were incubated in standard culture media for 40– 48 h. The expressed b-galactosidase was visualized in X-gal staining as described [16]. For enzyme assays, cells in 6-well plates were lysed in reporter lysis buffer and assayed for the enzyme activity according to the manufacturerÕs instructions (Promega). "
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    • ". Joung et al., (2000) successfully transduced Schwann cells with adenoviruses in vitro and in vivo, demonstrating LacZ gene expression for 5 weeks, during which nerve regeneration was accomplished in a rat model. In vitro studies of dorsal root ganglia sensory neurons of murine and human origin have demonstrated the successful transduction by recombinant adeno-associated adenovirus (rAAV) and vesicular stomatitis protein G-pseudotyped lentivirus vector derived from human immunodeficiency virus (HIV-1) [Fleming et al., 2001]. "
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