Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, 1 Yi Xue Yuan Road, Chongqing, 400016, China.
The People's Hospital of Rongchang District, Chongqing, 402460, China.
J Nanobiotechnology. 2022 Jan 6;20(1):27. doi: 10.1186/s12951-021-01233-4.
Currently, there are no curative drugs for hepatitis B virus (HBV). Complete elimination of HBV covalently closed circular DNA (cccDNA) is key to the complete cure of hepatitis B virus infection. The CRISPR/Cas9 system can directly destroy HBV cccDNA. However, a CRISPR/Cas9 delivery system with low immunogenicity and high efficiency has not yet been established. Moreover, effective implementation of precise remote spatiotemporal operations in CRISPR/Cas9 is a major limitation.
In this work, we designed NIR-responsive biomimetic nanoparticles (UCNPs-Cas9@CM), which could effectively deliver Cas9 RNP to achieve effective genome editing for HBV therapy. HBsAg, HBeAg, HBV pgRNA and HBV DNA along with cccDNA in HBV-infected cells were found to be inhibited. These findings were confirmed in HBV-Tg mice, which did not exhibit significant cytotoxicity and minimal off-target DNA damage.
The UCNPs-based biomimetic nanoplatforms achieved the inhibition of HBV replication via CRISPR therapy and it is a potential system for efficient treatment of human HBV diseases.
目前，尚无治疗乙型肝炎病毒 (HBV) 的药物。彻底消除 HBV 共价闭合环状 DNA (cccDNA) 是乙型肝炎病毒感染完全治愈的关键。CRISPR/Cas9 系统可直接破坏 HBV cccDNA。然而，尚未建立具有低免疫原性和高效率的 CRISPR/Cas9 递送系统。此外，CRISPR/Cas9 精确远程时空操作的有效实施是一个主要限制。
在这项工作中，我们设计了近红外响应仿生纳米颗粒 (UCNPs-Cas9@CM)，它可以有效传递 Cas9 RNP 以实现 HBV 治疗的有效基因组编辑。在 HBV 感染的细胞中发现 HBsAg、HBeAg、HBV pgRNA 和 HBV DNA 以及 cccDNA 受到抑制。在 HBV-Tg 小鼠中证实了这些发现，这些小鼠没有表现出明显的细胞毒性和最小的脱靶 DNA 损伤。
基于 UCNPs 的仿生纳米平台通过 CRISPR 治疗实现了 HBV 复制的抑制，这是一种治疗人类 HBV 疾病的有潜力的系统。
Zotero 插件
