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使用抗体偶联系统进行靶向基因治疗的高效核酸封装方法。

Highly efficient nucleic acid encapsulation method for targeted gene therapy using antibody conjugation system.

作者信息

Hong Seokbong, Jeong Seung-Hwan, Han Jang Hee, Yuk Hyeong Dong, Jeong Chang Wook, Ku Ja Hyeon, Kwak Cheol

机构信息

Department of Urology, Seoul National University College of Medicine, 03080 Seoul, South Korea.

Department of Urology, Seoul National University Hospital, 03080 Seoul, South Korea.

出版信息

Mol Ther Nucleic Acids. 2024 Sep 5;35(4):102322. doi: 10.1016/j.omtn.2024.102322. eCollection 2024 Dec 10.

Abstract

Gene therapy has surfaced as a promising avenue for treating cancers, offering the advantage of deliberate adjustment of targeted genes. Nonetheless, the swift degradation of nucleic acids in the bloodstream necessitates an effective and secure delivery system. The widespread utilization of poly(lactic-co-glycolic acid) (PLGA) nanoparticles as drug delivery systems has highlighted challenges in controlling particle size and release properties. Moreover, the encapsulation of nucleic acids exacerbates these difficulties due to the negatively charged surface of PLGA nanoparticles. In this study, we aimed to improve the encapsulation efficiency of nucleic acids by employing negatively charged microbeads and optimizing the timing of the specific formulation steps. Furthermore, by conjugating PSMA-617, a ligand for the prostate-specific membrane antigen (PSMA), with PLGA nanoparticles, we assessed the antitumor effects and the efficacy of a nucleic acid delivery system on a prostate cancer model. The employed technique within the nucleic acid encapsulation system represents a novel approach that could be adapted to encapsulate various kinds of nucleic acids. Moreover, it enables the attachment of targeting moieties to different cell membrane proteins, thereby unveiling new prospects for precise therapeutics in cancer therapy.

摘要

基因疗法已成为治疗癌症的一条有前景的途径,具有可精准调控靶向基因的优势。然而,血液中核酸的快速降解需要一个有效且安全的递送系统。聚乳酸-羟基乙酸共聚物(PLGA)纳米颗粒作为药物递送系统的广泛应用凸显了控制粒径和释放特性方面的挑战。此外,由于PLGA纳米颗粒带负电的表面,核酸的封装加剧了这些困难。在本研究中,我们旨在通过使用带负电的微珠并优化特定配方步骤的时间来提高核酸的封装效率。此外,通过将前列腺特异性膜抗原(PSMA)的配体PSMA-617与PLGA纳米颗粒偶联,我们评估了核酸递送系统对前列腺癌模型的抗肿瘤作用和疗效。核酸封装系统中采用的技术是一种新颖的方法,可用于封装各种核酸。此外,它能够将靶向部分连接到不同的细胞膜蛋白上,从而为癌症治疗中的精准治疗开辟了新前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96d9/11447337/3822ad53e66e/fx1.jpg

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