Protection of photoreceptors in a mouse model of RP10.
Recombinant adeno-associated viral (rAAV) vectors have recently been widely used for the delivery of therapeutic transgenes in preclinical and clinical studies for inherited retinal degenerative diseases. Interchanging capsid genes between different AAV serotypes has enabled selective delivery of transgene into specific cell type(s) of the retina. The RP10 form of autosomal dominant retinitis pigmentosa (adRP) is caused by missense mutations within the gene encoding inosine 5'-monophosphate dehydrogenase type 1. Here, we report that the use of rAAV2/5 vectors expressing shRNA targeting mutant IMPDH1 prevents photoreceptor degeneration, and preserves synaptic connectivity in a mouse model of RP10.
Tam
Lawrence C S
LC
Department of Genetics, Trinity College Dublin, Dublin 2, Ireland. lawrenct@tcd.ie
Kiang
Anna-Sophia
AS
Chadderton
Naomi
N
Kenna
Paul F
PF
Campbell
Matthew
M
Humphries
Marian M
MM
Farrar
G Jane
GJ
Humphries
Pete
P
D000818:Animals; D019610:Cytoprotection; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D016153:Genes, Suppressor; D006367:HeLa Cells; D006801:Humans; D007168:IMP Dehydrogenase / Q000235:genetics / Q000378:metabolism; D051379:Mice; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D020419:Photoreceptor Cells, Vertebrate / Q000201:enzymology / Q000473:pathology*; D011995:Recombination, Genetic / Q000235:genetics; D012174:Retinitis Pigmentosa / Q000201:enzymology / Q000473:pathology*; D013489:Suppression, Genetic; D013569:Synapses / Q000378:metabolism
D050505:Mutant Proteins; D007168:IMP Dehydrogenase; C463299:IMPDH1, mouse