PPP1R1B and Huntington disease: Previous studies with shRNAs showed equivalent silencing efficacy of the chimeric HTT constructs in rats and HEK-293T cells compared with silencing of the endogenous full-length human HTT in HD-derived neuronal cultures, suggesting that accessibility of silencing agents to the chimeric HTT constructs resembles the natural situation.23 Moreover, the rapid severity of DARPP-32-associated neuronal dysfunction challenges the read-out efficacy; but on the other hand, it strengthens confidence in case efficacy is demonstrated.