Prolonged biologically active transgene expression driven by HSV LAP2 in brain in vivo

Molecular Therapy : the Journal of the American Society of Gene Therapy
Veljko PuskovicD J Fink

Abstract

Herpes simplex virus (HSV) naturally establishes a life-long latent state in neurons, characterized by the expression of latency-associated transcripts (LATs) in the absence of viral lytic functions, and the latency-associated promoter (LAP2) has been identified as a moveable element responsible for the expression of LATs from latent HSV genomes. Prolonged transgene expression will be required for the treatment of chronic diseases of the CNS using HSV vectors. We therefore examined the ability of LAP2 to drive prolonged expression of a biologically active transgene from latent HSV vector genomes in brain in vivo using the 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models of Parkinson disease. A replication-incompetent HSV vector containing the glial cell-derived neurotrophic factor (GDNF) under the control of LAP2 was injected into the substantia nigra and 5 and a half months later 6-OHDA was injected into the striatum. GDNF expression from the vector preserved dopaminergic function measured by histology and behavior 6 months after vector inoculation. Mice inoculated with the LAP2-GDNF replication-incompetent HSV vector followed by 3 months of daily low-dose MPTP injections were substanti...Continue Reading

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Citations

Oct 9, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Joseph C Glorioso, David J Fink
Nov 22, 2005·Expert Opinion on Drug Delivery·Tom H JohnstonJonathan M Brotchie
Jun 7, 2012·Neurobiology of Disease·William F GoinsJoseph C Glorioso
Aug 25, 2009·Journal of Neuroscience Methods·Alessandro PapaleRiccardo Brambilla
Jun 24, 2008·European Journal of Pain : EJP·Shuanglin HaoDavid J Fink
Oct 19, 2004·Annual Review of Microbiology·Joseph C Glorioso, David J Fink
Mar 31, 2007·Pain·Darren WolfeJoseph C Glorioso
Sep 5, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Veljko PuskovicMarina Mata
Aug 27, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·B K BergesN W Fraser
Jun 2, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Munmun ChattopadhyayDavid J Fink
Oct 8, 2004·Gene Therapy·J FradetteJ C Glorioso
Oct 18, 2005·Muscle & Nerve·Thais Federici, Nicholas M Boulis
Jun 11, 2009·Nature Reviews. Neuroscience·Simon P Brooks, Stephen B Dunnett
May 12, 2007·Expert Review of Neurotherapeutics·James R GossJoseph C Glorioso
Nov 24, 2004·The Journal of Biological Chemistry·Radosveta P KoldamovaJohn S Lazo
Jun 8, 2021·Virology : Research and Treatment·Prapti H ModyJuliet V Spencer

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