UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

AAV-mediated knockdown of Peripherin-2 in vivo using miRNA-based hairpins

Georgiadis, A; Tschernutter, M; Bainbridge, JWB; Robbie, SJ; McIntosh, J; Nathwani, AC; Smith, AJ; (2010) AAV-mediated knockdown of Peripherin-2 in vivo using miRNA-based hairpins. GENE THER , 17 (4) 486 - 493. 10.1038/gt.2009.162.

Full text not available from this repository.

Abstract

Gene therapy for inherited retinal degeneration in which expression of a mutant allele has a gain-of-function effect on photoreceptor cells is likely to depend on efficient silencing of the mutated allele. Peripherin-2 (Prph2, also known as peripherin/RDS) is an abundantly expressed photoreceptor-specific gene. In humans, gain-of-function mutations in PRPH2 result in both autosomal dominant retinitis pigmentosa and dominant maculopathies. Gene-silencing strategies for these conditions include RNA interference by short hairpin RNAs (shRNAs). Recent evidence suggests that microRNA (miRNA)-based hairpins may offer a safer and more effective alternative. In this study, we used for the first time a virally transferred miRNA-based hairpin to silence Prph2 in the murine retina. The results show that an miRNA-based shRNA can efficiently and specifically silence Prph2 in vivo as early as 3 weeks after AAV2/8-mediated subretinal delivery, leading to a nearly 50% reduction of photoreceptor cells after 5 weeks. We conclude that miRNA-based hairpins can achieve rapid and robust gene silencing after efficient vector-mediated delivery to the retina. The rationale of using an miRNA-based template to improve the silencing efficiency of a hairpin may prove valuable for allele-specific silencing in which the choice for an RNAi target is limited and offers an alternative therapeutic strategy for the treatment of dominant retinopathies. Gene Therapy (2010) 17, 486-493; doi: 10.1038/gt.2009.162; published online 10 December 2009

Type: Article
Title: AAV-mediated knockdown of Peripherin-2 in vivo using miRNA-based hairpins
DOI: 10.1038/gt.2009.162
Keywords: RNAi, Prph2, AAV, miRNA, rds, retinal degeneration, DOMINANT RETINITIS-PIGMENTOSA, LEBERS CONGENITAL AMAUROSIS, GENE-THERAPY, RETINAL DEGENERATION, PHOTORECEPTOR CELLS, RNA INTERFERENCE, RIBOZYME RESCUE, MOUSE MODEL, RAT MODEL, MUTATIONS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/171237
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item