By a News Reporter-Staff News Editor at Gene Therapy Weekly -- Researchers detail new data in Biotechnology. According to news reporting out of Vancouver, Canada, by NewsRx editors, research stated, "Autosomal dominant diseases such as Huntington's disease (HD) are caused by a gain of function mutant protein and/or RNA. An ideal treatment for these diseases is to selectively suppress expression of the mutant allele while preserving expression of the wild-type variant."
Our news journalists obtained a quote from the research from the University of British Columbia, "RNase H active antisense oligonucleotides (ASOs) or small interfering RNAs can achieve allele selective suppression of gene expression by targeting single nucleotide polymorphisms (SNPs) associated with the repeat expansion. ASOs have been previously shown to discriminate single nucleotide changes in targeted RNAs with similar to 5-fold selectivity. Based on RNase H enzymology, we enhanced single nucleotide discrimination by positional incorporation of chemical modifications within the oligonucleotide to limit RNase H cleavage of the non-targeted transcript. The resulting oligonucleotides demonstrate > 100-fold discrimination for a single nucleotide change at an SNP site in the disease causing huntingtin mRNA, in patient cells and in a completely humanized mouse model of HD. The modified ASOs were also well tolerated after injection into the central nervous system of wild-type animals, suggesting that their tolerability profile is suitable for advancement as potential allele-selective HD therapeutics."
According to the news editors, the research concluded: "Our findings lay the foundation for efficient allele-selective downregulation of gene expression using ASOs-an outcome with broad application to HD and other dominant genetic disorders."
For more information on this research see: Rational design of antisense oligonucleotides targeting single nucleotide polymorphisms for potent and allele selective suppression of mutant Huntingtin in the CNS. Nucleic Acids Research, 2013;41(21):9634-9650. Nucleic Acids Research can be contacted at: Oxford Univ Press, Great Clarendon St, Oxford OX2 6DP, England. (Oxford University Press - www.oup.com/; Nucleic Acids Research - nar.oxfordjournals.org)
Our news journalists report that additional information may be obtained by contacting M.E. Ostergaard, University of British Columbia, Child & Family Res Inst, Center Mol Med & Therapeut, Vancouver, BC V5Z 4H4, Canada. Additional authors for this research include A.L. Southwell, H. Kordasiewicz, A.T. Watt, N.H. Skotte, C.N. Doty, K. Vaid, E.B. Villanueva, E.E. Swayze, C.F. Bennett, M.R. Hayden and P.P. Seth (see also technology.html">Biotechnology).
Keywords for this news article include: Antisense Technology, Biotechnology, Canada, Genetics, Vancouver, Neurology, Neurosurgery, Therapeutics, Bioengineering, British Columbia, Huntington's Disease, North and Central America, Central Nervous System Tumors, Central Nervous System Diseases
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