在活体中使用CRISPR编辑PCSK9可持续降低灵长类动物的胆固醇
Kiran Musunuru1,2,3, Alexandra C Chadwick4, Taiji Mizoguchi4
1Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Nature
|May 20, 2021
概括
通过脂质纳米颗粒传递的CRISPR基因编辑器在非人类灵长类动物中实现了持久的基因编辑. 这项研究支持降低胆固醇和心血管疾病的潜在一次性治疗.
科学领域:
- 生物技术
- 遗传学
- 分子生物学
背景情况:
- 像CRISPR-Cas这样的基因编辑技术提供了永久性遗传疾病修改的潜力.
- 在非人类灵长类动物中展示持久的编辑对于将体内基因疗法推向临床试验至关重要.
研究的目的:
- 在Cynomolgus子中使用脂质纳米颗粒来证明体内CRISPR基编辑的有效性和精度.
- 在临床前模型中评估基因编辑的耐用性及其治疗效果.
主要方法:
- 在体内向Cynomolgus子提供与脂质纳米颗粒复合的CRISPR基编辑器.
- 监测基因淘汰 (PCSK9),血脂水平 (LDL胆固醇) 和编辑的长期稳定性.
主要成果:
- 在一次脂质纳米颗粒输注后,在肝脏中实现了近乎完整的PCSK9基因敲除.
- 血中PCSK9水平降低了大约90%,LDL胆固醇降低了大约60%.
- 这些治疗效果在治疗后至少8个月保持稳定,表明持续的编辑.
结论:
- 通过脂质纳米颗粒传递的CRISPR基因编辑对于非人类灵长类动物肝脏的精确基因修饰是有效的.
- 这种方法支持治疗高胆固醇和动脉样性心血管疾病的潜在"一次性"策略.
- 这些发现为应用CRISPR基因编辑器在体内治疗点基因提供了概念证明.
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