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通过增强膜融合机制提高脂质转染效率。

Boosting Lipofection Efficiency Through Enhanced Membrane Fusion Mechanisms.

作者信息

Pavlov Rais V, Akimov Sergey A, Dashinimaev Erdem B, Bashkirov Pavel V

机构信息

Research Institute for Systems Biology and Medicine, 18 Nauchniy Proezd, Moscow 117246, Russia.

Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, 31/4 Leninskiy Prospekt, Moscow 119071, Russia.

出版信息

Int J Mol Sci. 2024 Dec 18;25(24):13540. doi: 10.3390/ijms252413540.

Abstract

Gene transfection is a fundamental technique in the fields of biological research and therapeutic innovation. Due to their biocompatibility and membrane-mimetic properties, lipid vectors serve as essential tools in transfection. The successful delivery of genetic material into the cytoplasm is contingent upon the fusion of the vector and cellular membranes, which enables hydrophilic polynucleic acids to traverse the hydrophobic barriers of two intervening membranes. This review examines the critical role of membrane fusion in lipofection efficiency, with a particular focus on the molecular mechanisms that govern lipoplex-membrane interactions. This analysis will examine the key challenges inherent to the fusion process, from achieving initial membrane proximity to facilitating final content release through membrane remodeling. In contrast to viral vectors, which utilize specialized fusion proteins, lipid vectors necessitate a strategic formulation and environmental optimization to enhance their fusogenicity. This review discusses recent advances in vector design and fusion-promoting strategies, emphasizing their potential to improve gene delivery yield. It highlights the importance of understanding lipoplex-membrane fusion mechanisms for developing next-generation delivery systems and emphasizes the need for continued fundamental research to advance lipid-mediated transfection technology.

摘要

基因转染是生物研究和治疗创新领域的一项基础技术。由于其生物相容性和膜模拟特性,脂质载体成为转染中的重要工具。将遗传物质成功递送至细胞质取决于载体与细胞膜的融合,这使得亲水性多核酸能够穿越两层间隔膜的疏水屏障。本综述探讨了膜融合在脂质体转染效率中的关键作用,特别关注调控脂质体-膜相互作用的分子机制。该分析将研究融合过程中固有的关键挑战,从实现初始膜接近到通过膜重塑促进最终内容物释放。与利用特殊融合蛋白的病毒载体不同,脂质载体需要进行策略性配方设计和环境优化以增强其融合性。本综述讨论了载体设计和促进融合策略的最新进展,强调了它们提高基因递送产量的潜力。它突出了理解脂质体-膜融合机制对于开发下一代递送系统的重要性,并强调了持续进行基础研究以推进脂质介导的转染技术的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6574/11677079/32bdb5d83ab2/ijms-25-13540-g001.jpg

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