精确制备超分子球形核酸,用于核素向基因传递
Ming Chen1, Siyuan Miao1, Yaqi Zhang1
1State Key Laboratory of Biogeology and Environmental Geology, Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan, 430074, China.
Angewandte Chemie (International ed. in English)
|August 23, 2024
概括
研究人员开发了超分子球状核酸 (Supra-SNAs) 用于向基因调控. 这些新型结构增强了核酶抵抗,细胞吸收和瘤保留,为先进的核酸输送和治疗提供了一个有前途的平台.
科学领域:
- 纳米技术 纳米技术
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 球形核酸 (SNA) 具有针对性传递和基因调节的潜力.
- 目前的分子SNAs (m-SNAs) 由于单个序列设计存在局限性,限制了组合准和基因调控功能.
研究的目的:
- 开发第三代超分子SNA (Supra-SNA) 平台,具有针对性和基因调节的双重功能.
- 通过将向性阿普坦与基因调节性反感性寡核酸结合起来,设计Supra-SNA.
主要方法:
- 通过自组装构建的Supra-SNA,将AS1411的aptamer-modified adamantine用于核素向与HER2反感官功能化的β-cyclodextrin结合起来.
- 对核酶降解抵抗,细胞吸收,基因调节有效性和瘤保留的m-SNA前体进行了评估.
主要成果:
- 与m-SNA相比,Supra-SNAs显著增强了对核酶降解的抵抗力,改善了细胞吸收和优越的瘤保留.
- 通过PI3K/Akt通路实现了HER2蛋白过度表达的特定抑制,并诱导了通过PI3K/Akt通路的最佳细胞抑制和细胞亡.
结论:
- 超SNAs代表了一种新的平台,具有用于组合准和基因调节的增强性质.
- 超-SNAs的精确定义的分子架构有助于在分子层面进行结构-属性关系研究.
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