华西医学

华西医学

CRISPR/Cas9 技术在乙型肝炎病毒基因组抑制中的应用

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目前世界范围内有约 2.4 亿慢性乙型肝炎病毒(hepatitis B virus,HBV)感染者,HBV 感染是世界性的重大公共卫生难题。随着分子生物学工具的不断发展,目前第 3 代基因定点编辑技术 CRISPR/Cas9 作为热点已经广泛地应用于多种病毒的研究与实验性治疗中。该文简要回顾了 HBV 基因组的特点、基因编辑技术的发展及原理和 CRISPR/Cas9 在 HBV 基因组抑制中的研究现状及局限性。相对于锌指核糖核酸酶和转录激活因子样效应物核酸酶其他两种基因编辑技术,CRISPR/Cas9 技术极大地提高了基因编辑的能力。虽然目前仍属于概念证明阶段,但多数基础研究均证实了 CRISPR/Cas9 技术在体内外对 HBV 病毒基因组具有编辑能力并能降低其 DNA 复制与病毒蛋白的表达能力。在潜在安全风险及基因编辑载体的输送效率等问题得到解决后,CRISPR/Cas9 技术联合逆转录抑制药物的治疗将为 HBV 感染的临床治愈带来曙光。

关键词: CRISPR/Cas9; 乙型肝炎病毒; 基因组抑制; 基因编辑

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