Biomedical subjects

W F Goins

Publications and source records attributed to W F Goins.

38 records · Page 3Linked to original sources

PubMedDate not supplied

Effect of protease inhibitors on yield of HSV-1-based viral vectors.

The ability to obtain high titer replication-defective herpes simplex virus (HSV) recombinant vectors will dramatically affect their use in gene therapy clinical trials. A variety of techniques and reagents have been employed to increase the overall yield of the vector. The effects of protease inhibitors on the yield of an HSV-1-based viral vector were examined. Experiments were conducted using a commercial protease inhibitor cocktail typically used in mammalian cell culture for protein production. Contrary to our expectation for enhanced vector yield, the results showed a dramatic reduction in vector yield. Moreover, it was found that AEBSF is the only component in the protease cocktail responsible for the low vector yield. On the basis of our hypothesis regarding the mode of action of AEBSF, we suggest that it should not be included in protease inhibitor cocktails designed for use in cultures aimed at production of viral vectors derived from HSV-1 or possibly several other vectors.

Culture Media↗

PubMedDate not supplied

Advances in the development of herpes simplex virus-based gene transfer vectors for the nervous system.

Herpes simplex virus (HSV) is an attractive candidate vector for treatment of nervous system disease by gene therapy. Here we review molecular aspects of the natural biology of HSV as it relates to vector design and application. Although gene transfer and transient expression was readily achieved using first generation replication defective HSV vectors, these vectors did not provide for long-term transgene expression, a prerequisite for effective treatment of neurodegenerative disease. The principle impediments to effective use of HSV vectors are residual toxicity of non-replicating vectors and the silencing of transgene expression from persisting latent viral genomes in neurons. Recent advances suggest that vectors deleted for multiple immediate early viral genes provide a solution to both of these problems and thereby provide for the first time insight into methods for the effective design of useful gene vectors for central nervous system applications.

Animals↗