Herpesvirus-mediated systemic delivery of nerve growth factor.


Sustained systemic dissemination of therapeutic proteins from peripheral sites is an attractive prospect for gene therapy applications. Replication-defective genomic herpes simplex virus type 1 (HSV-1) vectors were evaluated for their ability to express nerve growth factor (NGF) as a model gene product both locally and systemically. Intra-articular inoculation of NGF expression vectors in rabbits resulted in significant increases in joint lavage and blood plasma NGF that persisted for 1 year. A rhesus macaque injected intra-articularly displayed a comparable increase in plasma NGF for at least 6 months, at which time the serum NGF levels of this animal were sufficient to cause differentiation of PC12 cells in culture, but not to increase footpad epidermis innervation. Long-term reporter transgene expression was observed primarily in ligaments, a finding confirmed by direct inoculation of patellar ligament. Patellar ligament inoculation with a NGF vector resulted in elevated levels of circulating NGF similar to those observed following intra-articular vector delivery. These results represent the first demonstration of sustained systemic release of a transgene product using HSV vectors, raising the prospect of new applications for HSV-1 vectors in the treatment of systemic disease.


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@article{Wolfe2001HerpesvirusmediatedSD, title={Herpesvirus-mediated systemic delivery of nerve growth factor.}, author={Darren P Wolfe and W F Goins and T. Kaplan and Saverio Capuano and Julie Fradette and Micheal Murphey-Corb and P D Robbins and Justus B Cohen and J C Glorioso}, journal={Molecular therapy : the journal of the American Society of Gene Therapy}, year={2001}, volume={3 1}, pages={61-9} }