RNAi过程中靶mRNA敲除的最佳脉冲干预策略

Optimal Impulsive Intervention Strategy for Target mRNA Knockout in RNAi Process

本文基于RNA干扰(RNAi)诱导基因沉默原理,建立在不确定时刻进行体外注射siRNA的RNAi机制模型,构建靶mRNA敲除的最优控制问题.通过寻找siRNA最佳的注射时间以及注射的剂量,以保障在治疗周期内把靶mRNA的数量控制在阈值之下并且使成本达到最低.这是一个非标准优化问题,我们通过时间尺度变换将其转换成标准的优化问题,然后设计算法求解.数值模拟结果表明,在本文提出的优化策略干扰下,受体内靶mRNA的数量低于干预前靶mRNA的最低水平.该研究结果能为RNAi技术在临床应用上提供可靠的理论基础.

Based on the principle of RNA interference(RNAi)inducing gene silencing,this paper introduces the RNAi mechanism model by injecting siRNA in vitro at unfixed time,and defines the optimal control problem of target mRNA knockout.In this paper,we look for the optimal injection time and dose of siRNA to ensure that the target mRNA can be controlled below the threshold and the cost is minimized during the treatment cycle.This is a non-standard optimization problem.We convert it into a standard optimization problem by time scale transformation,and then design an algorithm to solve it.The numerical simulation results show that under the interference of the optimization strategy proposed in this paper,the amount of target RNA in the receptor is lower than the lowest level of target RNA before intervention.Our results provide a reliable theoretical basis for the application of RNAi technology.