反义核酸基因治疗中电子计算机的辅助设计

Computer Aid Design of Antisense Oligonucleotide in Gene Therapy —— Review

本文概述了反义寡核苷酸作为基因治疗药物的状况 ,归纳了目前对妨碍反义寡核苷酸作为基因治疗药物取得快速进展的主要因素 :反义寡核苷酸作为基因治疗药物的有效性 ;反义寡核苷酸作为基因治疗药物的毒副作用。从细胞和基因水平详细介绍目前对这些影响因素的分析 :①反义寡核苷酸未能有效对靶基因的同源基因的鉴别是导致其毒副作用的主要原因。②靶基因的二、三级结构严重影响反义寡核苷酸达到靶位置。③影响反义寡核苷酸的传送和快速退火的问题。也介绍如何使用电子计算机方法对反义寡核苷酸的靶基因做全面分析 ,即对靶基因的二级结构和同源性分析 ,并最终设计出反义寡核苷酸 ,达到降低反义寡核苷酸作为治疗药物的毒副作用 ,提高治疗的有效性的目的。最后归纳出计算机辅助设计的方法。

In this paper,the situation on antisense oligonucleotide as a means of gene therapy was outlined,and the main factors impeding its progress at present was summarized. The one of main factors is the efficiency of antisense oligonucleotide as a drug and the other is the side-effect in clinical use. At the level of cell and gene, these influential factors were analyzed in detail. The main factor that makes side-effect in using antisense oligonucleotide is the difficulty to distinguish effectively homologous-gene from target gene. The another factor is the secondary structure and three-dimensional structure of target gene that seriously affect antisense oligonucleotide to arrive at target position. The third problem is what can affect antisense oligonucleotide transmission and quick annealing. How use computer technique to analyze fully the target gene of antisense oligonucleotide including the secondary structure and homology of target gene,and to design effective antisense oligonucleotide ,in order to reduce its side-effect in clinical use of antisense oligonucleotide as a drug of gene therapy,and the computer- aid design methed were described.