通过对氨基基基组进行生物可逆氨酸修饰 (BioRAM) 来进行原生蛋白质的细胞内传递
Jonathan Franke1,2, Jan Vincent V Arafiles1, Christian Leis1,2
1Department of Chemical Biology, Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Robert-Rössle-Strasse 10, 13125, Berlin, Germany.
Angewandte Chemie (International ed. in English)
|June 2, 2025
概括
研究人员开发了BioRAM,一种新的蛋白质修饰方法,可以将功能性蛋白质输送到人体细胞中. 这一战略克服了以前的交付挑战,使得基于蛋白质的治疗方法和研究工具的细胞内应用成为可能.
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 细胞生物学 细胞生物学
背景情况:
- 基于蛋白质的工具在准生物途径方面比小分子提供了优势.
- 由于脂质双层屏障,目前在将功能性蛋白质送入哺乳动物细胞方面存在局限性.
- 为了在医学和研究中得到更广泛的应用,需要一种通用的细胞内蛋白质输送方法.
研究的目的:
- 开发一种新的策略,以有效和生物可逆地将功能性蛋白质输入哺乳动物细胞的细胞质中.
- 为了使无基因工程蛋白质用于细胞内应用.
- 为了证明开发的交付系统的有效性和稳定性.
主要方法:
- 采用一种生物可逆的蛋白质修饰策略,使用含有短的酸 (BioRAM).
- 优化生物结合,以快速进行细胞内裂变和原生蛋白质恢复.
- 与细胞透 (CPP) 添加剂协议相结合,可提高输送效果.
- 在血清存在的情况下,测试光蛋白和功能性RNase A的输送效率.
主要成果:
- 生物RAM使得蛋白质在哺乳动物细胞中的有效细胞溶液输送成为可能.
- 生物结合策略确保了快速的细胞内分裂,并完全恢复了原生蛋白质的功能.
- 实现了光蛋白和功能性RNase A的卓越传递,导致生理反应.
- 生物RAM系统表现出有效的性能,即使存在血清.
结论:
- 生物RAM提供了一种多功能且有效的细胞内蛋白质输送方法,克服了以前的局限性.
- 这一策略显著扩大了基于蛋白质的工具在分子生物学和医学中的潜力.
- 将功能性蛋白质输送到细胞质中的能力为治疗干预和生物研究开辟了新的途径.
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