latest paper on the huntington's prospect for ddRNAi (eg uniqure). appears to suggest uniqure's work is via ddRNAi method :
siRNA does not undergo such processing, requires higher concentrations and frequent dosing to achieve comparable knockdown. Unprotected siRNA in the cytoplasm may be vulnerable to degradation and modifications that reduce on-target binding.
shRNA can be further optimized in the form of artificial pri-miRNA transcripts. This is achieved by by embedding the shRNA sequence into a miRNA context such as the miR-30 stem loop precursor. This method was used to inducibly control p35 levels in vitro and in vivo, even when the construct was present as a single genomic copy [29].
Based on this artificial pri-miRNA strategy, the Dutch gene therapy company UniQure has achieved mutant HTT allele-specific targeting via AAV5 in a humanized HD mouse model [30].
BLT Price at posting:
24.0¢ Sentiment: Hold Disclosure: Held
