Targeting huntingtin
نویسندگان
چکیده
منابع مشابه
CTG repeat-targeting oligonucleotides for down-regulating Huntingtin expression
Huntington's disease (HD) is a fatal, neurodegenerative disorder in which patients suffer from mobility, psychological and cognitive impairments. Existing therapeutics are only symptomatic and do not significantly alter the disease progression or increase life expectancy. HD is caused by expansion of the CAG trinucleotide repeat region in exon 1 of the Huntingtin gene (HTT), leading to the form...
متن کاملDiscovery of a novel small-molecule targeting selective clearance of mutant huntingtin fragments.
CAG-triplet repeat extension, translated into polyglutamines within the coding frame of otherwise unrelated gene products, causes 9 incurable neurodegenerative disorders, including Huntington's disease. Although an expansion in the CAG repeat length is the autosomal dominant mutation that causes the fully penetrant neurological phenotypes, the repeat length is inversely correlated with the age ...
متن کاملInhibition of mutant huntingtin expression by RNA duplex targeting expanded CAG repeats
The specific silencing of the gene of interest is the major objective of RNA interference technology; therefore, unique sequences but not abundant sequence repeats are targeted by silencing reagents. Here, we describe the targeting of expanded CAG repeats that occur in transcripts derived from the mutant allele of the gene implicated in Huntington's disease (HD) in the presence of the normal al...
متن کاملNuclear-targeting of mutant huntingtin fragments produces Huntington's disease-like phenotypes in transgenic mice.
Huntington's disease (HD) results from the expansion of a glutamine repeat near the N-terminus of huntingtin (htt). At post-mortem, neurons in the central nervous system of patients have been found to accumulate N-terminal fragments of mutant htt in nuclear and cytoplasmic inclusions. This pathology has been reproduced in transgenic mice expressing the first 171 amino acids of htt with 82 gluta...
متن کاملAllele-selective inhibition of mutant huntingtin expression with antisense oligonucleotides targeting the expanded CAG repeat.
Huntington's disease (HD) is a currently incurable neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat within the huntingtin (HTT) gene. Therapeutic approaches include selectively inhibiting the expression of the mutated HTT allele while conserving function of the normal allele. We have evaluated a series of antisense oligonucleotides (ASOs) targeted to the expanded ...
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ژورنال
عنوان ژورنال: Nature Structural & Molecular Biology
سال: 2014
ISSN: 1545-9993,1545-9985
DOI: 10.1038/nsmb.2758