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动态交联聚合物的单合成,用于输送血清耐性核酸

Zhisong Sun¹, Mengyao Ren¹, Bingchen Shan²

¹Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory of Carbon-Based Functional Materials and Devices, Soochow University, Suzhou 215123, China. lcyin@suda.edu.cn.

Biomaterials science

|July 11, 2023

概括

研究人员开发了一种新的三元聚合物,用于高效的核酸输送. 这种聚合物在血清中显示出优异的等离子体DNA和mRNA转染,从而使潜在的基因疗法应用能够有效地进行基因编辑.

科学领域:

生物材料科学生物材料科学
基因治疗基因治疗
聚合物化学聚合物化学

背景情况:

用于核酸输送的酸性聚合物面临着复杂合成,细胞内释放不良和血清稳定性低等挑战.
有效和稳定的非病毒载体对于推进基因疗法和基因工程应用至关重要.

研究的目的:

合成和评估一系列新的三元聚合物,以提高血清中的等离子体DNA和mRNA输送.
确定一种最佳的聚合物组成,以促进有效的核酸凝聚,细胞吸收和内解体释放.

主要方法:

使用一种简单的单绿色化学方法,通过动态交叉链接的乙二酸 (APBA),聚和低分子量聚乙烯胺 (PEI 1.8k) 来合成三元聚合物.
对各种多 (例如,鲁丁) 和APBA异构体 (例如,2-APBA) 的选,以确定表现最佳的聚合物.
优化聚合物 (2-PEI-RT) 对DNA凝聚,血清稳定性,细胞传染和CRISPR-Cas9基因组编辑效率的评估.

主要成果:

由路丁和2-APBA形成的三元聚合物2-PEI-RT,证明了高效的等离子体DNA凝聚和血清稳定性.
与PEI 25k相比,2-PEI-RT在瘤细胞中实现了更高的等离子体DNA转染效率 (1-3个数量级更高).
实现了Cas9mRNA和sgRNA的有效细胞溶液传递,导致显著的CRISPR-Cas9基因组编辑in vitro.

结论:

动态交联的三元聚合物2-PEI-RT为非病毒核酸输送提供了一个简单而强大的平台.
这种聚合物系统克服了传统的化聚合物的关键局限性,为基因疗法和基因工程展示了巨大的前景.
聚合物的pH敏感降解在内酶体中促进了有效的货物释放,并增强了基因编辑结果.

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