合成聚合物辅助反义寡核苷酸递送:精准疾病治疗的靶向方法

Synthetic-polymer-assisted antisense oligonucleotide delivery: targeted approaches for precision disease treatment.

作者信息

Alvarez Ana Cubillo, Maguire Dylan, Brannigan Ruairí P

机构信息

School of Chemical Sciences, Dublin City University, Glasnevin, Dublin 9, Ireland.

出版信息

Beilstein J Nanotechnol. 2025 Mar 27;16:435-463. doi: 10.3762/bjnano.16.34. eCollection 2025.

Abstract

This review explores the recent advancements in polymer-assisted delivery systems for antisense oligonucleotides (ASOs) and their potential in precision disease treatment. Synthetic polymers have shown significant promise in enhancing the delivery, stability, and therapeutic efficacy of ASOs by addressing key challenges such as cellular uptake, endosomal escape, and reducing cytotoxicity. The review highlights key studies from the past decade demonstrating how these polymers improve gene silencing efficiencies, particularly in cancer and neurodegenerative disease models. Despite the progress achieved, barriers such as immunogenicity, delivery limitations, and scalability still need to be overcome for broader clinical application. Emerging strategies, including stimuli-responsive polymers and advanced nanoparticle systems, offer potential solutions to these challenges. The review underscores the transformative potential of polymer-enhanced ASO delivery in personalised medicine, emphasising the importance of continued innovation to optimise ASO-based therapeutics for more precise and effective disease treatments.

摘要

本综述探讨了用于反义寡核苷酸(ASO)的聚合物辅助递送系统的最新进展及其在精准疾病治疗中的潜力。合成聚合物通过解决细胞摄取、内体逃逸和降低细胞毒性等关键挑战,在提高ASO的递送、稳定性和治疗效果方面显示出巨大的前景。该综述重点介绍了过去十年的关键研究,展示了这些聚合物如何提高基因沉默效率,特别是在癌症和神经退行性疾病模型中。尽管已取得进展,但免疫原性、递送限制和可扩展性等障碍仍需克服,以便更广泛地应用于临床。新兴策略,包括刺激响应性聚合物和先进的纳米颗粒系统,为这些挑战提供了潜在的解决方案。该综述强调了聚合物增强ASO递送在个性化医学中的变革潜力,强调持续创新对于优化基于ASO的疗法以实现更精确、有效的疾病治疗的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6690/11956074/9d9b93805a49/Beilstein_J_Nanotechnol-16-435-g002.jpg

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