Viral vectors for in vivo gene transfer in Parkinson's disease: properties and clinical grade production

Abstract

Because Parkinson's disease is a progressive degenerative disorder that is mainly confined to the basal ganglia, gene transfer to deliver therapeutic molecules is an attractive treatment avenue. The present review focuses on direct in vivo gene transfer vectors that have been developed to a degree that they have been successfully used in animal model of Parkinson's disease. Accordingly, the properties of recombinant adenovirus, recombinant adeno-associated virus, herpes simplex virus, and lentivirus are described and contrasted. In order for viral vectors to be developed into clinical grade reagents, they must be manufactured and tested to precise regulatory standards. Indeed, clinical lots of viral vectors can be produced in compliance with current Good Manufacturing Practices (cGMPs) regulations using industry accepted manufacturing methodologies, manufacturing controls, and quality systems. The viral vector properties themselves combined with physiological product formulations facilitate long-term storage and direct in vivo administration.

Figure 1

Approximate number of viral vector related publications regarding Parkinson’s disease over a period of years. The data is based on pubmed searches for each year. The rAAV publications exclude Ad publications. The data includes review publications. The data may not be perfectly accurate due to the nature of pubmed search terms but is intended to show the trend of increased publications since 1984.

Figure 2

A schematic of generalized production procedures of viral vectors for experimental use. There are minor differences that are unique to individual laboratories and this figure is not intended to be used as an exact protocol for recombinant virus production.