Extracellular vesicle mimetics as delivery vehicles for oligonucleotide-based therapeutics and plasmid DNA.

IF 4.3 3区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Frontiers in Bioengineering and Biotechnology Pub Date : 2024-10-17 eCollection Date: 2024-01-01 DOI:10.3389/fbioe.2024.1437817

Anastasiya Oshchepkova, Ivan Chernikov, Svetlana Miroshnichenko, Olga Patutina, Oleg Markov, Innokenty Savin, Yaroslav Staroseletz, Mariya Meschaninova, Pavel Puchkov, Sergey Zhukov, Maxim Kupryushkin, Mikhail Maslov, Aleksandra Sen'kova, Valentin Vlassov, Elena Chernolovskaya, Marina Zenkova

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引用次数: 0

Abstract

Introduction: Small membrane particles called extracellular vesicles (EVs) transport biologically active cargo between cells, providing intercellular communication. The clinical application of EVs is limited due to the lack of scalable and cost-effective approaches for their production and purification, as well as effective loading strategies.

Methods: Here we used EV mimetics produced by cell treatment with the actin-destabilizing agent cytochalasin B as an alternative to EVs for the delivery of therapeutic nucleic acids.

Results: Cytochalasin-B-inducible nanovesicles (CINVs) delivered a fully modified N-(methanesulfonyl)- or mesyl (µ-) antisense oligonucleotide to B16 melanoma cells, selectively decreasing the level of target microRNA-21 with effectiveness comparable to that observed upon Lipofectamine 2000-mediated delivery. The efficiency of the CINV-mediated delivery of plasmid DNA encoding EGFP varied depending on the type of recipient cells. Surprisingly, under experimental conditions, CINVs were unable to deliver both modified and natural short RNA duplexes-small interfering RNA and immunostimulatory RNA-probably due to their poor loading into CINVs.

Discussion: CINVs demonstrated unique properties for the delivery of therapeutic nucleic acids, especially for antisense oligonucleotide-based therapy.

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细胞外囊泡模拟物作为寡核苷酸治疗药物和质粒 DNA 的输送载体。

简介被称为细胞外囊泡（EVs）的小膜颗粒在细胞间运输具有生物活性的货物，提供细胞间的交流。方法：在这里，我们使用细胞经肌动蛋白稳定剂细胞松弛素 B 处理后产生的模拟 EV，作为 EV 的替代品来递送治疗性核酸：结果：细胞松弛素B诱导的纳米颗粒（CINVs）将完全修饰的N-（甲磺酰基）-或甲磺酰基（µ-）反义寡核苷酸递送到B16黑色素瘤细胞，选择性地降低了靶microRNA-21的水平，其效果与Lipofectamine 2000介导的递送效果相当。CINV 介导的编码 EGFP 的质粒 DNA 的递送效率因受体细胞类型而异。令人惊讶的是，在实验条件下，CINVs 无法递送修饰的和天然的短 RNA 双链体--小干扰 RNA 和免疫刺激 RNA--这可能是由于它们在 CINVs 中的负载能力较差：讨论：CINVs 在递送治疗性核酸，尤其是基于反义寡核苷酸的治疗方面表现出独特的特性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Bioengineering and Biotechnology Chemical Engineering-Bioengineering

CiteScore

8.30

自引率

5.30%

发文量

2270

审稿时长

12 weeks

期刊介绍： The translation of new discoveries in medicine to clinical routine has never been easy. During the second half of the last century, thanks to the progress in chemistry, biochemistry and pharmacology, we have seen the development and the application of a large number of drugs and devices aimed at the treatment of symptoms, blocking unwanted pathways and, in the case of infectious diseases, fighting the micro-organisms responsible. However, we are facing, today, a dramatic change in the therapeutic approach to pathologies and diseases. Indeed, the challenge of the present and the next decade is to fully restore the physiological status of the diseased organism and to completely regenerate tissue and organs when they are so seriously affected that treatments cannot be limited to the repression of symptoms or to the repair of damage. This is being made possible thanks to the major developments made in basic cell and molecular biology, including stem cell science, growth factor delivery, gene isolation and transfection, the advances in bioengineering and nanotechnology, including development of new biomaterials, biofabrication technologies and use of bioreactors, and the big improvements in diagnostic tools and imaging of cells, tissues and organs. In today`s world, an enhancement of communication between multidisciplinary experts, together with the promotion of joint projects and close collaborations among scientists, engineers, industry people, regulatory agencies and physicians are absolute requirements for the success of any attempt to develop and clinically apply a new biological therapy or an innovative device involving the collective use of biomaterials, cells and/or bioactive molecules. “Frontiers in Bioengineering and Biotechnology” aspires to be a forum for all people involved in the process by bridging the gap too often existing between a discovery in the basic sciences and its clinical application.