ABSTRACT
This chapter discusses some considerations for planning in vivo studies, especially for a particular class of therapeutics acting through the RNA interference (RNAi) pathway. The design of RNAi therapeutics can be computationally modeled and validated against the desired targets and verified for no off-target effects with various software platforms. Formulations of RNAi therapeutics studied in vivo include doses as low as 0.05 mg/kg, and as high as 24 mg/kg, and commonly range between 1 and 5 mg/kg dose. In vivo studies can determine the biodistribution, cytotoxicity, and efficacy of the drug. Additionally, the possibility of using a delivery agent needs to be carefully considered as well, as it can greatly affect the properties and characteristics of the therapeutic in vivo. There are various ways to define in vivo toxicity, but generally toxicity is regarded as an undesired effect at the cellular, tissue, or organism level.
