Herpes Simplex Virus (HSV-1) vector have great potential for gene therapy of neurological diseases and for studies in basic neuroscience. For example, HSV-1 vectors that express tyrosine hydroxylase have supported long-term (1 year) biochemical and behavioral correction of the 6-hydorxydopamine (6-OHDA) rat model of Parkinson's disease. However, these vectors have been complicated by side effects, such as cytopathic effects and immune responses, caused principally by the helper virus. Therefore, this laboratory recently developed a helper virus-free packaging system for these vectors. This system substantially addresses many of the previous problems with the vector system, but suffer from low titers. Therefore, this fellowship proposes two different approaches to increase the titers of the helper virus-free vector system. And then additional experiments will be performed to use these increased titers, in combination with improved vectors for expressing catecholamine biosynthetic enzymes, to correct the 6-OHDA rat model of PD.
| Yang, T; Zhang, G R; Zhang, W et al. (2001) Enhanced reporter gene expression in the rat brain from helper virus-free HSV-1 vectors packaged in the presence of specific mutated HSV-1 proteins that affect the virion. Brain Res Mol Brain Res 90:1-16 |
| Sun, M; Lee, J; Yu, L et al. (2000) Modest increases in the titers of helper virus-free herpes simplex virus 1 (HSV-1) vectors by packaging in a cell line with inducible expression of HSV-1 VP16 or by treatment with N,N'-hexamethylene-bis-acetamide. Acta Virol 44:365-9 |
| Sun, M; Zhang, G R; Yang, T et al. (1999) Improved titers for helper virus-free herpes simplex virus type 1 plasmid vectors by optimization of the packaging protocol and addition of noninfectious herpes simplex virus-related particles (previral DNA replication enveloped particles) to the packagin Hum Gene Ther 10:2005-11 |
