用于增强基因传递的高度支化聚（β-氨基酯）的新优化策略：去除小分子量组分,Polymers

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用于增强基因传递的高度支化聚（β-氨基酯）的新优化策略：去除小分子量组分
Polymers ( IF 4.7 ) Pub Date : 2023-03-18 , DOI: 10.3390/polym15061518
Yinghao Li ₁ , Xianqing Wang ₁ , Zhonglei He ₁ , Zishan Li ₁ , Melissa Johnson ₁ , Bei Qiu ₁ , Rijian Song ₁ , Sigen A ₁ , Irene Lara-Sáez ₁ , Jing Lyu ₁ , Wenxin Wang ₁

Affiliation

高度支化的聚（β-氨基酯）（HPAE）已成为最有前途的非病毒基因递送载体候选者之一。与其他基因传递载体相比，HPAE 具有广泛的分子量分布 (MWD)。尽管为优化 HPAE 以增强基因传递为目标做出了重大努力，但很少研究不同分子量 (MW) 组分对转染的影响。在这项工作中，提出了一种新的结构优化策略，以增强 HPAE 基因转染为目标。通过逐步沉淀方法获得一系列具有不同 MW 组分的 HPAE，并将其应用于质粒 DNA 递送。已证明从原始 HPAE 结构中去除小分子量成分可以显着提高其转染性能（例如，GFP 表达在 w/w 为 10/1 时增加 7 倍）。通过将其扩展到具有不同 MW 和不同分支度的不同 HPAE 系统，证明了该策略的普遍性，其中转染性能在去除小 MW 部分后表现出均匀的幅度增强。这项工作为开发高效 HPAE 基因递送载体开辟了一条新途径，并为理解 HPAE 结构-性质关系提供了新的见解，这将促进 HPAE 在基因治疗临床应用中的转化。

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A New Optimization Strategy of Highly Branched Poly(β-Amino Ester) for Enhanced Gene Delivery: Removal of Small Molecular Weight Components

Highly branched poly(β-amino ester) (HPAE) has become one of the most promising non-viral gene delivery vector candidates. When compared to other gene delivery vectors, HPAE has a broad molecular weight distribution (MWD). Despite significant efforts to optimize HPAE targeting enhanced gene delivery, the effect of different molecular weight (MW) components on transfection has rarely been studied. In this work, a new structural optimization strategy was proposed targeting enhanced HPAE gene transfection. A series of HPAE with different MW components was obtained through a stepwise precipitation approach and applied to plasmid DNA delivery. It was demonstrated that the removal of small MW components from the original HPAE structure could significantly enhance its transfection performance (e.g., GFP expression increased 7 folds at w/w of 10/1). The universality of this strategy was proven by extending it to varying HPAE systems with different MWs and different branching degrees, where the transfection performance exhibited an even magnitude enhancement after removing small MW portions. This work opened a new avenue for developing high-efficiency HPAE gene delivery vectors and provided new insights into the understanding of the HPAE structure–property relationship, which would facilitate the translation of HPAEs in gene therapy clinical applications.

更新日期：2023-03-18

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