Abstract
The ability to inhibit expression of a mutant allele while retaining expression of a wild-type protein might provide a useful approach to treating Huntington's Disease (HD) and other inherited pathologies. The mutant form of huntingtin (HTT), the protein responsible for HD, is encoded by an mRNA containing an expanded CAG repeat. We demonstrate that peptide nucleic acid conjugates and locked nucleic acids complementary to the CAG repeat selectively block expression of mutant HTT. The selectivity of inhibition is at least as good as that shown by a small interfering RNA targeted to a deletion polymorphism. Our data suggest that antisense oligomers are promising subjects for further development as an anti-HD therapeutic strategy.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Alleles
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Humans
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Huntingtin Protein
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Huntington Disease / therapy*
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Nerve Tissue Proteins / antagonists & inhibitors*
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Nerve Tissue Proteins / genetics
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Nuclear Proteins / antagonists & inhibitors*
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Nuclear Proteins / genetics
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Oligonucleotides / chemistry
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Oligonucleotides / genetics*
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Oligonucleotides / therapeutic use
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Peptide Nucleic Acids / chemistry
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Peptide Nucleic Acids / genetics*
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Peptide Nucleic Acids / therapeutic use
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RNA, Small Interfering / chemistry
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RNA, Small Interfering / genetics*
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RNA, Small Interfering / therapeutic use
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Selection, Genetic
Substances
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HTT protein, human
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Huntingtin Protein
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Nerve Tissue Proteins
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Nuclear Proteins
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Oligonucleotides
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Peptide Nucleic Acids
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RNA, Small Interfering
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locked nucleic acid