Targeting adenoviral transgene expression to neurons.

Molecular and Cellular Neurosciences
Karen SimsAnn Logan

Abstract

Adenovirus (Ad) is an efficient and safe vector for CNS gene delivery since it infects non-replicating neurons and does not cause insertional mutagenesis of host cell genomes. However, the promiscuous Ad CAR receptor targets cells non-specifically and activates a host immune response. Using Ad5 containing an expression cassette encoding the gene for green fluorescent protein, gfp, regulated by the neuron specific promoter synapsin-1 and the woodchuck post-transcriptional regulatory element (WPRE), we demonstrate efficient, prolonged and promoter-restricted gfp expression in neurons of mixed primary adult rat dorsal root ganglion (DRG) and retinal cell cultures. We also demonstrate restricted gfp expression in DRG neurons after direct injections of Ad5 containing the synapsin-1(gfp)/WPRE construct into L4 DRG in vivo, while Ad5 CMV(gfp) transfected both DRG glia and neurons. Moreover, since the effective titres of delivered Ad5 are reduced with this neuron specific promoter/WPRE expression cassette, the viral immune challenge should be attenuated when used in vivo.

References

Feb 1, 1983·Journal of Neurocytology·A RambourgA Beaudet
Feb 9, 1996·The Journal of Biological Chemistry·S SchochG Thiel
Apr 21, 2001·Molecular and Cellular Neurosciences·M BerryA Baird
Jul 18, 2006·Molecular and Cellular Neurosciences·Andrew P HibbertDavid R Kaplan
May 17, 2007·Current Neurovascular Research·Marios G LykissasAlexandros E Beris

❮ Previous
Next ❯

Citations

Jun 18, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jieming ZengShu Wang
Jun 24, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·David H StitelmanTimothy R Brazelton
Jul 20, 2012·Biochemical and Biophysical Research Communications·Katherine J D A ExcoffonChristopher J Benson
Nov 20, 2009·Anesthesia and Analgesia·Nancy A Nussmeier, Bruce E Searles

❮ 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.