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携带外源性干扰RNA混合物的间充质干细胞衍生外泌体在新冠疫情爆发时代是一种前所未有的治疗方法。

MSC-derived exosomes carrying a cocktail of exogenous interfering RNAs an unprecedented therapy in era of COVID-19 outbreak.

作者信息

Jamalkhah Monire, Asaadi Yasaman, Azangou-Khyavy Mohammadreza, Khanali Javad, Soleimani Masoud, Kiani Jafar, Arefian Ehsan

机构信息

Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran.

School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

J Transl Med. 2021 Apr 22;19(1):164. doi: 10.1186/s12967-021-02840-3.

Abstract

BACKGROUND

The onset of the SARS-CoV-2 pandemic has resulted in ever-increasing casualties worldwide, and after 15 months, standard therapeutic regimens are yet to be discovered.

MAIN BODY

Due to the regenerative and immunomodulatory function of MSCs, they can serve as a suitable therapeutic option in alleviating major COVID-19 complications like acute respiratory distress syndrome. However, the superior properties of their cognate exosomes as a cell-free product make them preferable in the clinic. Herein, we discuss the current clinical status of these novel therapeutic strategies in COVID-19 treatment. We then delve into the potential of interfering RNAs incorporation as COVID-19 gene therapy and introduce targets involved in SARS-CoV-2 pathogenesis. Further, we present miRNAs and siRNAs candidates with promising results in targeting the mentioned targets.

CONCLUSION

Finally, we present a therapeutic platform of mesenchymal stem cell-derived exosomes equipped with exogenous iRNAs, that can be employed as a novel therapeutic modality in COVID-19 management aiming to prevent further viral spread within the lung, hinder the virus life cycle and pathogenesis such as immune suppression, and ultimately, enhance the antiviral immune response.

摘要

背景

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)大流行的爆发已导致全球范围内的伤亡人数不断增加,且在15个月后,仍未找到标准的治疗方案。

正文

由于间充质干细胞(MSCs)具有再生和免疫调节功能,它们可作为缓解主要的2019冠状病毒病(COVID-19)并发症(如急性呼吸窘迫综合征)的合适治疗选择。然而,其同源外泌体作为一种无细胞产物的优越特性使其在临床上更受青睐。在此,我们讨论这些新型治疗策略在COVID-19治疗中的当前临床状况。然后,我们深入探讨干扰RNA掺入作为COVID-19基因治疗的潜力,并介绍参与SARS-CoV-2发病机制的靶点。此外,我们展示了在靶向上述靶点方面取得有前景结果的微小RNA(miRNAs)和小干扰RNA(siRNAs)候选物。

结论

最后,我们提出了一个配备外源性干扰RNA的间充质干细胞衍生外泌体治疗平台,其可作为COVID-19管理中的一种新型治疗方式,旨在防止病毒在肺内进一步传播,阻碍病毒生命周期和发病机制(如免疫抑制),并最终增强抗病毒免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e6b/8063313/1f08ab7bdc5b/12967_2021_2840_Fig1_HTML.jpg

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