Therapeutic gene silencing in neurological disorders, using interfering RNA.
The development of interfering RNA (RNAi) from a naturally occurring phenomenon to a tool for mediating highly specific gene silencing provides an exciting prospect as a novel therapeutic strategy for a wide range of disorders. Although the efficacy of RNAi as a research tool for analysing gene function has been well demonstrated in several cell types, the therapeutic potential of RNAi-mediated gene silencing has only recently started to be investigated. Several neurodegenerative disorders provide particularly suitable candidates for RNAi based therapy; however, many hurdles preclude the success of therapeutic application. These include the challenge of delivering active RNAi molecules to the specific target cell populations where they are required and appropriate regulation of gene suppression, such as to maintain a long-lasting therapeutic effect. Furthermore, for safety reasons, off-target effects should be minimised. Here we review the advancement of RNAi technology for therapeutic application and highlight the potential of targeted gene silencing for the treatment of neurodegenerative diseases.
Ralph
G Scott
GS
Oxford Biomedica, Ltd., Medawar Centre, Robert Robinson Avenue, Oxford Science Park, OX4 4GA Oxford, UK.
Mazarakis
Nicholas D
ND
Azzouz
Mimoun
M
D000690:Amyotrophic Lateral Sclerosis / Q000628:therapy; D020868:Gene Silencing; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D009422:Nervous System Diseases / Q000628:therapy*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000627:therapeutic use*
D012333:RNA, Messenger; D034741:RNA, Small Interfering