Efficacy in siRNA therapies depends on the mechanisms that drive the delivery of siRNA to target cell, the interactions of siRNA with RNA interference machinery and the downstream effects of the reduction in target mRNA. To understand the impact of these mechanisms on the efficacy of a siRNA therapy quantitatively and to guide the optimization of dosing regimen a mechanistic PK-PD model was developed based on literature data from preclinical and clinical studies. In this talk the outcomes from the model analysis and simulations will be summarized that provided insights about (1) the key processes that contribute to the variability and uncertainty in target mRNA suppression and downstream target reduction during siRNA therapy, (2) the impact of dosing regimen on the efficacy of the siRNA therapy and (3) the importance of the characteristics of siRNA therapy and target mRNA and protein in defining the therapy limitations.
list the key biological processes that contribute to the efficacy of siRNA therapies
describe the impact of dosing regimen on the efficacy of the siRNA therapy
describe the importance of the characteristics of siRNA therapy, target mRNA and target protein in defining the siRNA therapy limitations