氨基酸功能化聚合甲基胺载体用于siRNA转染,其基因是聚-2-异-2-氧沙) 的修饰
Florica Adriana Jerca1, Cristina Muntean2, Katrien Remaut2
1Smart Organic Materials Group, "Costin D. Nenitzescu" Institute of Organic and Supramolecular Chemistry, Romanian Academy, 202B Spl. Independentei CP 35-108, 060023 Bucharest, Romania; Supramolecular Chemistry Group, Centre of Macromolecular Chemistry (CMaC), Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281-S4, B-9000 Ghent, Belgium.
概括
具有氨基酸侧链的新型多-2-异-2-氧沙) (PiPOx) 共聚物有效地在体外输送siRNA用于基因沉默. 这些生物材料表现出高的转染效率和强大的基因沉默,在不影响细胞活力的情况下超过商业标准.
科学领域:
- 聚合物化学 聚合物化学
- 生物材料科学 生物材料科学
- 基因传递 基因传递
背景情况:
- 功能性聚合物,如聚二异二氧化 (PiPOx),对于开发先进的智能生物材料至关重要.
- PiPOx为定制生物材料特性提供了多功能合成和聚合后修饰.
研究的目的:
- 为了合成和描述基于PiPOx的新型阴离子聚合甲基胺与氨基酸侧链用于siRNA复合和体外转化.
- 为了研究PiPOx修饰与N-Boc-L-氨基酸的动力学,并开发具有受控水友性/疏水性平衡的共聚物.
主要方法:
- 用N-Boc-L-氨基酸修改PiPOx的环开放添加反应.
- 解除N-Boc受保护的聚合物的保护,以产生阳离子 (协同) 聚合物.
- 使用FT-IR,1H NMR,SEC,TGA-DSC-MS和极度测量进行了表征.
- 评估siRNA复杂化,体外转化效率,基因沉默功效和细胞活性的评估.
主要成果:
- PiPOx成功地被各种N-Boc-L-氨基酸修饰,并确定了反应动力学.
- 含有托和瓦林或林侧链的阴阳性共聚合物在体外表现出高的转染效率 (>90%的细胞).
- 这些共聚物实现了强大的基因沉默 (IC50降至5.5nM),表现优于商业JetPRIME®,没有观察到细胞活力的减少.
结论:
- 以PiPOx为基础的带有特定氨基酸侧链的化共聚合物在体外siRNA传递和基因沉默方面非常有效.
- 开发的共聚合物代表了先进基因治疗应用的有希望的生物材料.
- 该系统与现有的商业传染剂相比,在没有毒性问题的情况下提供了更高的性能.
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