This one from the French research institutes just published overnight. A good read. It references both Katherine High and Beverly Davidson's work in the field, and notes the limitations of Alny style siRNA and ISIS style ASO as therapeutic candidates for the CNS diseases.
"Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder resulting from polyglutamine expansion in the huntingtin (HTT) protein and for which there is no cure. Although suppression of both wild type and mutant HTT expression by RNA interference is a promising therapeutic strategy, a selective silencing of mutant HTT represents the safest approach preserving WT HTT expression and functions. We developed small hairpin RNAs (shRNAs) targeting single nucleotide polymorphisms (SNP) present in the HTT gene to selectively target the disease HTT isoform. Most of these shRNAs silenced, efficiently and selectively, mutant HTT in vitro.
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These findings provide evidence of the therapeutic potential of allele-specific RNA interference for HD."
