Adenovirus-mediated transfer of a functional GAD gene into nerve cells: potential for the treatment of neurological diseases

Gene Therapy
J J RobertG Le Gal La Salle

Abstract

The recent development of efficient virus-mediated gene transfer into nerve cells allows the prospect of new strategies for the treatment of drug-resistant neurological diseases. Some forms of epilepsy may be amenable to gene therapy. Although there is no obvious candidate gene, the consensual GABA hypothesis of epilepsy suggests that the GAD gene may be beneficial. GAD gene expression may be useful in supplying the inhibitory neurotransmitter GABA to particular critical brain territories. We show herein that a nonreplicative recombinant adenovirus carrying the GAD67 gene under the control of Rous sarcoma virus long terminal repeat promoter is able to express the transgene in primary cultures of neurons and glial cells. Expression of the GAD67 gene was assessed by immunoblotting and immunohistochemical analysis. We demonstrated the functionality of the transgene, the expression of which resulted in production of large amounts of GABA in neuronal and glial cell cultures. Substantial production of the enzyme was also detected for several weeks in infected organotypic slices cultured from new-born rat hippocampal tissues. The virally encoded GAD67 was also expressed in vivo in various brain areas involved in various neurological d...Continue Reading

Citations

Feb 11, 1999·Journal of Neuroscience Research·G M Smith, M I Romero
Aug 24, 2004·Cell and Tissue Research·O Eberhardt, J B Schulz
Oct 22, 2003·Neurosurgery Clinics of North America·Mary E Garrity-MosesNicholas M Boulis
Aug 23, 2008·Epilepsia·Véronique RibanMatthew J During
Nov 27, 2002·Journal of Neurosurgery·Nicholas M BoulisEva L Feldman
Jul 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·C R OzawaR M Sapolsky
May 1, 2003·Expert Review of Neurotherapeutics·Heng ZhaoGary K Steinberg
Dec 12, 2001·Molecular Therapy : the Journal of the American Society of Gene Therapy·P Factor
Jan 19, 2000·Gene Therapy·H J Federoff
Jan 4, 2003·Nature Reviews. Neuroscience·Robert M Sapolsky
Feb 16, 2000·Gene Therapy·L C CostantiniO Isacson
Apr 24, 2007·American Journal of Physical Medicine & Rehabilitation·Shearwood McClellandNicholas M Boulis
Jul 21, 2001·Annals of the New York Academy of Sciences·M A YenariG K Steinberg
Mar 28, 2021·Journal of Neuroscience Methods·Ruth Butler-Ryan, Ian C Wood

❮ Previous
Next ❯

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.