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通过生物导向进化识别的向骨髓输送RNA的纳米粒子
Cory D Sago1, Melissa P Lokugamage1, Fatima Z Islam1
1Wallace H. Coulter Department of Biomedical Engineering , Georgia Institute of Technology , Atlanta , Georgia 30332 , United States.
Journal of the American Chemical Society
|November 6, 2018
概括
研究人员开发了一种新的条形码系统,以追踪纳米粒子在体内的传递. 这导致了BM1的发现,它是一种脂质纳米粒子 (LNP),可以有效地将基因编辑工具传递给骨髓内皮细胞 (BMEC).
科学领域:
- 生物医学工程
- 纳米技术
- 基因治疗
背景情况:
- 骨髓内皮细胞 (BMEC) 是造血干细胞微环境的关键调节者.
- BMEC是基因编辑和siRNA治疗的重要目标,但有效的系统传递仍然是一个挑战.
- 现有的 in vitro 纳米颗粒查没有发现具有特定 BMEC 热带性的候选物.
研究的目的:
- 开发一种用于在体内量化功能性siRNA传递给BMEC的系统.
- 确定能够将siRNA和sgRNA传递给BMEC的新型纳米粒子.
- 了解纳米粒子化学组成和BMEC向之间的关系.
主要方法:
- 开发了一种独特的条形码系统来量化单个小鼠中的100多个纳米粒子的功能性细胞质siRNA输送.
- 使用生物信息学和体内定向进化来识别BMEC向的纳米粒子.
- 分析了已识别的纳米颗粒的化学组成,包括脂质纳米颗粒 (LNP) 尺寸,聚乙烯糖醇结构和胆固醇含量.
主要成果:
- 鉴定了BM1,一种新的脂质纳米粒子 (LNP),在体内向BMEC传递有效的siRNA和sgRNA.
- 发现BMEC热带性与LNP大小无关,但受到聚乙烯糖醇结构和胆固醇的显著影响.
- 证明LNP的简单化学修饰可以在没有活性向对象的情况下赋予显著的血管向能力.
结论:
- 开发的体内功能查系统成功识别了BM1,这是第一个能够有效地向BMEC传递siRNA和sgRNA的纳米粒子.
- 这项研究强调了体内查在纳米粒子中发现复杂结构-热带关系的潜力.
- 简单的纳米颗粒化学修饰提供了一个可行的策略,以实现体内有针对性的输送.
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