传统的以病毒DNA为载体的基因治疗方法存在病毒导入的靶向性差、整合位点的特异性差、基因剂量的可控性差以及病毒载体具有一定的免疫原性的缺点,而实际上许多单基因遗传病只要将突变的单个碱基校正就能达到基因治疗的目的,不必置换或整合入整个基因.嵌合修复术(chimerplasty)是近年来迅速发展起来的一种基因定位修复技术,该技术利用RNA/DNA嵌合体分子与要修复的宿主染色体DNA碱基序列互补而精确定位并原位修复,也可用于人工定点突变,已在单基因遗传病的基因治疗及植物遗传改良等方面获得了成功的应用.介绍了该技术的原理、应用举例及前景.
The problems existing in the conventional gene therapy involves low effectivity in virus′ targeting transduction, low speciality in integration, low effectivity in controlling the gene expression dosage and immunogenicity of virus vector. While most single gene genopathies can be cured by correct the single mutant nucleotide using gene therapy, without changing the whole gene. Chimeraplasty is a tool for site-specific gene repairing which developed rapidly in recent years. The RNA/DNA chimeric oligonucleotide can located to the exact site and repair the wrong base in situ by complementing to the host chromosome DNA sequence,and it can also be used to produce targeted mutation. It has been successfully applied in the gene therapy of some single gene genopathy and plant genetical modification. The principle, examples and prospect of this technique was described.
欧阳立明,张嗣良,刘志敏.基因定位修复技术——嵌合修复术(chimeraplasty)[J].生物化学与生物物理进展,2001,28(3):322-325
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