Beijing National Laboratory for Molecular Science, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Biomater Sci. 2021 Oct 26;9(21):7024-7033. doi: 10.1039/d1bm00790d.
The discovery of CRISPR/Cas9 genome-editing technology enables the precise manipulation of mammalian DNA sequences for treating genetic disorders. Despite its high efficiency for genome editing, the introduction of CRISPR/Cas9 machinery, which is composed of Cas9 nuclease protein and guide RNA, into cells challenges its clinical translation potential. Therefore, the intracellular delivery of genome-editing machinery determines the efficacy of gene manipulation the CRISPR/Cas9 technology. Recently, metallosupramolecules including metal-organic frameworks (MOFs) and metal-organic cages (MOCs) have been designed to selfassemble with Cas9 nuclease and guide RNA for CRISPR/Cas9 delivery and genome editing. Herein, we review the most recent advances and strategies of constructing metallosupramolecules for CRISPR/Cas9 delivery. In particular, we discuss nanoscale MOFs and MOCs that could be assembled and regulated by the intracellular environment for the spatiotemporal delivery of genome editing machinery. We also provide a perspective view of the future development of metallosupramolecules for genome editing and gene therapy .
CRISPR/Cas9 基因组编辑技术的发现使精确操纵哺乳动物 DNA 序列治疗遗传疾病成为可能。尽管 CRISPR/Cas9 基因组编辑技术具有很高的效率，但将 Cas9 核酸酶蛋白和指导 RNA 组成的 CRISPR/Cas9 机械引入细胞中，挑战了其临床转化的潜力。因此，基因组编辑机械在细胞内的传递决定了基因操作的效率，即 CRISPR/Cas9 技术。最近，包括金属-有机骨架（MOFs）和金属-有机笼（MOCs）在内的金属超分子已被设计用于与 Cas9 核酸酶和指导 RNA 自组装，以实现 CRISPR/Cas9 的传递和基因组编辑。在此，我们综述了用于 CRISPR/Cas9 传递的最新金属超分子构建进展和策略。特别是，我们讨论了可以通过细胞内环境组装和调节的纳米级 MOFs 和 MOCs，以实现基因组编辑机械的时空传递。我们还对金属超分子用于基因组编辑和基因治疗的未来发展提供了展望。
