基于ATP敏感的协体,用于细胞内输送治疗性寡核酸
Tatiana Vedekhina1,2, Vladislav Anufriev3, Nicole Polischuk4
1Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia.
Frontiers in molecular biosciences
|March 2, 2026
概括
研究人员开发了新的ATP敏感协体,以改善细胞内核酸治疗药物的输送. 这些同体对寡核酸 (ODN) 输送有前途,克服了先前在拆装效率方面的限制.
科学领域:
- 分子医学是分子医学.
- 生物技术是生物技术.
- 药物输送系统 药物输送系统
背景情况:
- 对DNA/RNA疗法的细胞内传递至关重要,但具有挑战性.
- 现有的载体,如脂和纳米颗粒,存在稳定性,有效性或毒性问题.
- 基于的协生物提供了优势,但遭受了低效的细胞内解封.
研究的目的:
- 开发一种新的基于的协系统,具有编程的细胞内药物释放.
- 为了改造ATP响应性协体,以增强核酸的输送.
- 评估这些协同体对寡核酸 (ODN),等离子体DNA和mRNA输送的疗效.
主要方法:
- 设计了具有ATP响应模块的内在无序的胺丰富.
- 通过将与RNA,ODN,等离子体DNA或mRNA混合组装的协同生.
- 使用光显微镜监测同体形成和动态.
- 在HEK293细胞中评估细胞吸收和细胞内释放.
主要成果:
- 在没有ATP的条件下和在ATP的存在下部分ODN释放中表现出稳定性.
- 在4个小时内,同细胞成功地透到HEK293细胞中,并在20小时内将ODN释放到细胞质中.
- 对ATP敏感的协体在ODN传递方面表现优于对ATP不敏感的对照体,但在等离子体DNA和mRNA传递方面表现劣.
结论:
- 对ATP敏感的联体代表了一种用于编程释放核酸疗法的新方法.
- 这些同生物显示出作为输送寡核酸的载体的巨大潜力.
- 为了更高效地传递更大的核酸,如等离子体DNA和mRNA,需要进一步优化.
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