基于类转录激活因子效应物(TALEs)的基因组定点操控技术
Transcription activator-like effectors(TALEs)based genome engineering
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摘要: 基于类转录激活因子效应物(transcription activator-like effectors,TALEs)的基因组定点操控技术能够对基因组功能体系的反向遗传操作于基因及转录水平进行精确操控。TALEs 是来源于植物病原菌—黄单胞杆菌(Xanthomonas spp.)的DNA结合蛋白,其结合域通常由包含34 个氨基酸残基的重复模块串联而成。根据编码规则,可人为重新编排重复模块顺序使其能够识别新的DNA 序列。该人工设计TALEs 对基因组的定点操控(包括转录调控和基因组编辑)已在体外培养的人类细胞和多种模式生物中得到了成功应用,为模式生物基因功能研究,农作物性状改善及人类遗传性疾病治疗等开辟了新时代。Abstract: Systematic reverse-engineering of functional genome architecture requires precise modifications of gene sequences and transcription levels. The development and application of transcription activator-like effectors(TALEs) has created a wealth of genome engineering possibilities. TALEs are a class of naturally occurring DNA-binding proteins found in the plant pathogen Xanthomonas species. The DNA-binding domain of each TALE typically consists of tandem 34-amino acid repeat modules rearranged according to a simple cipher to target new DNA sequences. Customized TALEs can be used for a wide variety of genome engineering applications, including transcriptional modulation and genome editing. Such "genome engineering" has now been established in human cells and a number of model organisms, thus opening the door to better understanding gene function in model organisms, improving traits in crop plants and treating human genetic disorders.