通过微凝聚剂介导的mRNA细胞内输液,通过等离子体膜输入mRNA
Yoshimasa Kawaguchi1, Ayumi Kikkawa1, Seigo Kimura1,2
1Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto, 611-0011, Japan.
Angewandte Chemie (International ed. in English)
|November 18, 2025
概括
研究人员开发了微凝聚物,一种新的无脂质纳米颗粒平台,使用和核酸进行细胞内输送. 这种方法使得有效的信使RNA (mRNA) 传递和蛋白质表达 in vivo,显示疫苗和癌症治疗的希望.
科学领域:
- 生物技术是生物技术.
- 分子生物学分子生物学
- 药物输送系统 药物输送系统
背景情况:
- 脂质纳米颗粒 (LNP) 对于核酸输送是常见的,但具有局限性.
- 开发无LNP平台对于推进细胞内传递技术至关重要.
- 酸核酸协体为有效的基因传递提供了潜在的替代方案.
研究的目的:
- 开发一种新的无LNP平台,用于使用酸核酸微凝结物的细胞内核酸输送.
- 为了证明微凝聚物的可行性,以传递信使RNA (mRNA),小干扰RNA (siRNA) 和等离子体DNA (pDNA) 在体外和体内.
- 为了优化微凝聚物形成,以便有效地输送核酸和随后的蛋白质表达.
主要方法:
- 微米大小的协体 (微密集体) 的形成,使用化FcB(L17E) 3和核酸 (siRNA,mRNA,pDNA).
- 在体外评估通过基因敲除siRNA传递效率.
- 在小鼠体内皮下注射微冷凝剂以评估蛋白质表达.
主要成果:
- FcB(L17E) 3与siRNA形成微凝聚物,实现40%的基因淘汰.
- 添加单链DNA (ssDNA) 能够形成mRNA微凝聚物和随后的蛋白质表达.
- 优化的微冷凝剂促进了pDNA的传递.
- 在小鼠体内诱导蛋白质表达的微冷凝剂的皮下注射.
结论:
- 微凝聚物代表了一个可行的无LNP平台,用于细胞内输送各种核酸.
- 这一策略使得在体内有效的mRNA传递和蛋白质表达成为可能.
- 微冷凝技术有可能用于癌症免疫疗法和基于mRNA的疫苗接种.
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