Fig. 1.
From: Editorial focus: understanding off-target effects as the key to successful RNAi therapy
Schematic representation of the RNAi drug discovery and development process. Full mechanistic understanding of the disease allows selection of highly disease specific therapy targets, and thus early elimination of off-targets. In the first phase, candidate sequence design and optimization allows early hazard identification and elimination, whereas chemical modifications can be applied to design out potential hazards and limitations. Furthermore, in later phases potential liabilities regarding delivery system choice should be assessed. Finally, broad pharmacological profiles of the lead drug candidates should be obtained, before drug candidates undergo further clinical development