Research and Clinical Translation Center of Gene Medicine and Tissue Engineering, School of Public Health, Anhui University of Science and Technology, Huainan 232001, China.
Charles Institute of Dermatology, School of Medicine, University College Dublin, Dublin D04 V1W8, Ireland.
ACS Appl Mater Interfaces. 2023 Aug 2;15(30):36667-36675. doi: 10.1021/acsami.3c05010. Epub 2023 Jul 21.
Gene therapy has emerged as a significant advancement in medicine in recent years. However, the development of effective gene delivery vectors, particularly polymer vectors, remains a significant challenge. Limited understanding of the internal structure of polymer vectors has hindered efforts to enhance their efficiency. This work focuses on investigating the impact of polymer structure on gene delivery, using the well-known polymeric vector poly(β-amino ester) (PAE) as a case study. For the first time, we revealed the distinct characteristics of individual polymer components and their synergistic effects-the appropriate combination of different components within a polymer (high MW and low MW components) on gene delivery. Additionally, artificial intelligence (AI) analysis was employed to decipher the relationship between the polymer component distribution (PCD) and gene transfection performance. Guided by this analysis, a series of highly efficient polymer vectors that outperform current commercial reagents such as jetPEI and Lipo3000 were developed, among which the transfection efficiency of the PAE-B1-based polyplex was approximately 1.5 times that of Lipo3000 and 2 times that of jetPEI in U251 cells.
近年来，基因治疗已成为医学领域的重大进展。然而，有效的基因传递载体（特别是聚合物载体）的开发仍然是一个重大挑战。对聚合物载体内部结构的有限了解阻碍了提高其效率的努力。本工作重点研究聚合物结构对基因传递的影响，以众所周知的聚合物载体聚（β-氨基酯）（PAE）作为案例研究。我们首次揭示了聚合物中各个组成部分的独特特性及其协同作用——聚合物内不同组成部分（高 MW 和低 MW 成分）的适当组合对基因传递的影响。此外，还利用人工智能（AI）分析来破译聚合物成分分布（PCD）与基因转染性能之间的关系。通过这项分析，开发出了一系列高效的聚合物载体，其性能优于当前的商业试剂，如 jetPEI 和 Lipofectamine 3000，其中基于 PAE-B1 的聚阳离子的转染效率在 U251 细胞中比 Lipofectamine 3000 高约 1.5 倍，比 jetPEI 高 2 倍。
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