CRISPR-Cas9

CRISPR-Cas9 is involved in viral defense mechanisms of bacteria which recognize and destroy foreign DNA. CRISPR-Cas9 is involved in the excision of CAG repeats to make harmless alleles and silence the mHTT expression by insertion of stop codon/missense mutations [68,108–110]. In HD140Q-knockin mice, it was demonstrated that CRISPR-Cas9 can be used to reduce mHTT and improve motor function, but not to increase the lifespan of these mice [69]. Ekman et al. showed that CRISPR-Cas9 can be used for mHTT editing, which can extend survival and improve motor function in the R6 mice following intrastriatal delivery [111].

#### 3.7.2. RNA Targeting Therapies

The four major methods to inhibit the function of mHTT mRNA are: ASOs, RNAi compounds, novel viral vectors, and small-molecule splicing modulators.
