A transgenic mouse model for gene therapy of rhodopsin-linked Retinitis Pigmentosa.
Mutational heterogeneity in genes causative of dominantly inherited disorders represents a significant barrier for development of therapies directed towards correction of the primary genetic defect. To circumvent the mutational heterogeneity present in rhodopsin- (RHO-) linked autosomal dominant Retinitis Pigmentosa (adRP), a strategy involving suppression and replacement of RHO has been adopted. RNA interference- (RNAi-) mediated suppression of RHO has been explored as has the generation of an RNAi-resistant replacement gene using the degeneracy of the genetic code. Additionally, the functional equivalence of codon-modified replacement genes has been demonstrated in a transgenic animal (RHO-M). Suppression and replacement, while exemplified by adRP, may also be relevant to many other dominantly inherited diseases with the hallmark of mutational heterogeneity.
O'Reilly
Mary
M
Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland. oreillym@tcd.ie
Millington-Ward
Sophia
S
Palfi
Arpad
A
Chadderton
Naomi
N
Cronin
Thérèse
T
McNally
Niamh
N
Humphries
Marian M
MM
Humphries
Peter
P
Kenna
Paul F
PF
Farrar
G Jane
GJ
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004596:Electroretinography; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D012243:Rhodopsin / Q000096:biosynthesis / Q000235:genetics*
D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012243:Rhodopsin