School of Physical Education, Hangzhou Normal University, Hangzhou 311121, China.
Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA.
Int J Mol Sci. 2022 Aug 6;23(15):8750. doi: 10.3390/ijms23158750.
The designer nucleases, including Zinc Finger Nuclease (ZFN), Transcription Activator-Like Effector Nuclease (TALEN), and Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated (CRISPR/Cas), have been widely used for mechanistic studies, animal model generation, and gene therapy development. Clinical trials using designer nucleases to treat genetic diseases or cancers are showing promising results. Despite rapid progress, potential off-targets and host immune responses are challenges to be addressed for in vivo uses, especially in clinical applications. Short-term expression of the designer nucleases is necessary to reduce both risks. Currently, delivery methods enabling transient expression of designer nucleases are being pursued. Among these, virus-like particles as delivery vehicles for short-term designer nuclease expression have received much attention. This review will summarize recent developments in using virus-like particles (VLPs) for safe delivery of gene editing effectors to complement our last review on the same topic. First, we introduce some background information on how VLPs can be used for safe and efficient CRISPR/Cas9 delivery. Then, we summarize recently developed virus-like particles as genome editing vehicles. Finally, we discuss applications and future directions.
设计型核酸酶，包括锌指核酸酶（ZFN）、转录激活因子样效应核酸酶（TALEN）和规律成簇间隔短回文重复/CRISPR 相关（CRISPR/Cas），已被广泛用于机制研究、动物模型生成和基因治疗开发。使用设计型核酸酶治疗遗传疾病或癌症的临床试验正在取得有希望的结果。尽管取得了快速进展，但潜在的脱靶效应和宿主免疫反应是体内应用（特别是临床应用）需要解决的挑战。短期表达设计型核酸酶对于降低这两个风险是必要的。目前，正在寻求能够瞬时表达设计型核酸酶的递送方法。其中，病毒样颗粒作为短期设计型核酸酶表达的递送载体引起了广泛关注。本综述将总结最近利用病毒样颗粒（VLPs）安全递送达基因编辑效应物的进展，补充我们上次关于该主题的综述。首先，我们介绍了 VLPs 如何用于安全有效的 CRISPR/Cas9 递送的一些背景信息。然后，我们总结了最近开发的作为基因组编辑载体的病毒样颗粒。最后，我们讨论了应用和未来方向。
