Team:NJU-China/RNAi

model

2. RNAi module

2.1 Introduction

    RNA interference (RNAi) is a major tool for transiently suppressing the expression of genes. Many mathematical models have been constructed to elucidate the mechanism of RNA interference and provide accurate predictions. Nevertheless, most of the current models focus merely on RNAi and fail to consider the delivery process. We modeled the delivery process and the input variant in this module should be the output result of the delivery module.

    A challenge for the successful clinical application of RNAi-based drugs is determining the dosing schedule required for efficacy. Patients may ask the following questions: How soon will RNAi-based drugs take to exert efficacy after injection? How long will the efficacy last? What is the dose I need to take, and will it be too costly? How soon will the level of Mu opioid receptor (MOR) protein recover? Is RNAi therapy safe enough? Mathematical modeling using simple kinetic equations for each step in the RNAi process can shed light on many of these questions.

2.2 Model methods

    This model is inspired by the paper written by Bartlett and Davis [1]. The system uses the presence of the RISC complex, which is formed in exosomes and escaped from endosome, as a stable source to provide silencing power. Then, the RISC units are targeted to mRNA having the same sequence as the siRNA that triggers this process, binding with mRNA to form an activated RISC-mRNA complex. Once bound to complementary mRNA, activated RISC may induce the degradation of mRNA and further silence protein expression.