Fig. 5
From: RNAi mechanisms in Huntington’s disease therapy: siRNA versus shRNA
Negative feedback loop mechanism. If the promoter of HTT is used to drive the shRNA construct, a stoichiometric equivalent of shRNA may be expressed to neutralize mHTT levels. A similar strategy may be employed for constructs activated during autophagy and lysosomal biogenesis, such as PGC1a. Then, the shRNA will be expressed when HTT aggregates have formed to induce autophagy or clearance – shRNA on demand and only when required by the cell