Virus-delivered small RNA silencing sustains strength in amyotrophic lateral sclerosis.
Mutations in superoxide dismutase cause a subset of familial amyotrophic lateral sclerosis and provoke progressive paralysis when expressed in mice. After retrograde transport to the spinal cord following injection into muscles, an adeno-associated virus carrying a gene that encodes a small interfering RNA was shown to target superoxide dismutase messenger RNA for degradation. The corresponding decrease in mutant superoxide dismutase in spinal motor neurons preserved grip strength. This finding provides proof of principle for the selective reduction of any neuronal protein and supports intramuscular injections of a small interfering RNA-encoding virus as a viable therapy for this type of familial amyotrophic lateral sclerosis.
Miller
Timothy M
TM
Ludwig Institute for Cancer Research, University of California, San Diego, USA.
Kaspar
Brian K
BK
Kops
Geert J
GJ
Yamanaka
Koji
K
Christian
Lindsey J
LJ
Gage
Fred H
FH
Cleveland
Don W
DW
D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D000229:Dependovirus / Q000235:genetics; D020868:Gene Silencing; D015316:Genetic Therapy; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D018737:Hand Strength / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000503:physiopathology; D020125:Mutation, Missense; D034741:RNA, Small Interfering / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D014162:Transfection
D034741:RNA, Small Interfering; C000606290:SOD1 protein, human; D049452:Green Fluorescent Proteins; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1