Department of Orthopedics, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, Guangdong, 518035, China.
Guangdong Provincial Research Center for Artificial Intelligence and Digital Orthopedic Technology, Shenzhen Second People's Hospital, Shenzhen, Guangdong, 518035, China.
Biomater Sci. 2023 May 30;11(11):3762-3783. doi: 10.1039/d2bm01636b.
RISPR-Cas9 has exhibited enormous potential in gene therapy. It can perform genome editing with single-nucleotide precision in various types of cell and tissue, providing a powerful breakthrough technology for genome editing in therapeutic development. But the limited delivery methods pose substantial challenges pertinent to safe and effective CRISPR/Cas9 delivery, thus hindering its application. These challenges should be tackled to develop next-generation genetic therapies. Biomaterial-based drug delivery systems can overcome these issues, for example using biomaterials as carriers for CRISPR/Cas9 targeted delivery, and conditional control of its function can improve precision, furnish on-demand and transient gene editing and reduce adverse consequences such as off-target events and immunogenicity, representing a promising direction for modern precision medicine. This review describes the application status and research progress of current CRISPR/Cas9 delivery approaches, including polymeric nanoparticles, liposomes, extracellular vesicles, inorganic nanoparticles and hydrogels. The unique properties of light-controlled and small-molecule drugs for spatially and temporally controlled genome editing are also illustrated. In addition, targetable delivery vehicles for the active delivery of CRISPR systems are also discussed. The perspectives to overcome the current limitations in the CRISPR/Cas9 delivery and their bench-to-bedside translation are also highlighted.
CRISPR-Cas9 在基因治疗中展现出巨大的潜力。它可以在各种类型的细胞和组织中进行单核苷酸精度的基因组编辑，为治疗性开发中的基因组编辑提供了强大的突破性技术。但有限的递送方法对安全有效的 CRISPR/Cas9 递送提出了实质性的挑战，从而阻碍了其应用。这些挑战需要得到解决，才能开发下一代基因治疗方法。基于生物材料的药物递送系统可以克服这些问题，例如使用生物材料作为 CRISPR/Cas9 靶向递送的载体，并对其功能进行条件控制，从而提高精度，提供按需和瞬时的基因编辑，并减少脱靶事件和免疫原性等不良反应，代表了现代精准医学的一个有前途的方向。本文描述了当前 CRISPR/Cas9 递送方法的应用现状和研究进展，包括聚合物纳米粒子、脂质体、细胞外囊泡、无机纳米粒子和水凝胶。还说明了光控小分子药物在时空可控基因组编辑方面的独特性质。此外，还讨论了用于 CRISPR 系统主动递送的靶向递送载体。还强调了克服 CRISPR/Cas9 递送当前限制并将其从实验室转化为临床的观点。
