Recombinant Adeno-associated Viral Vectors as Therapeutic Agents to Treat Neurological Disorders

doi:doi:10.1016/j.ymthe.2005.11.009

Molecular Therapy (2006) 13, 463–483; doi: 10.1016/j.ymthe.2005.11.009

Recombinant Adeno-associated Viral Vectors as Therapeutic Agents to Treat Neurological Disorders

Ronald J. Mandel^1,2, Fredric P. Manfredsson^1,2, Kevin D. Foust^2,3, Aaron Rising^1,2, Sharon Reimsnider^1,2, Kevin Nash^2,4 and Corinna Burger^2,4

¹Department of Neuroscience, and McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL 32610, USA
²Powell Gene Therapy Center, and McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL 32610, USA
³Department of Pediatrics, and McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL 32610, USA
⁴Department of Molecular Genetics and Microbiology, and McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL 32610, USA

Correspondence: Ronald J. Mandel, Department of Neuroscience, University of Florida College of Medicine, P.O. Box 100244, Gainesville, FL 32610, USA. Fax: +1 352 392 8347. E-mail: rmandel@ufl.edu

Received 22 September 2005; Revised 12 November 2005; Accepted 13 November 2005.

Top

Abstract

Recombinant adeno-associated virus (rAAV) is derived from a small human parvovirus with an excellent safety profile. In addition, this viral vector efficiently transduces and supports long-term transgene expression in the nervous system. These properties make rAAV a reasonable candidate vector for treating neurological disorders. Indeed, rAAV is currently being used in five early stage clinical trials for various neurodegenerative disorders. Therefore, we will review the currently available preclinical data using rAAV in animal models of central nervous system (CNS) disorders. Moreover, potential caveats for rAAV-based gene therapy in the CNS are also presented.