Herpesvirus-mediated systemic delivery of nerve growth factor.

Abstract

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.

Statistics

0100200300'03'05'07'09'11'13'15'17
Citations per Year

316 Citations

Semantic Scholar estimates that this publication has 316 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@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} }