Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
BMC Biotechnol. 2021 Mar 10;21(1):20. doi: 10.1186/s12896-021-00683-w.
Over the past decade, therapeutic messenger RNAs (mRNAs) have emerged as a highly promising new class of drugs for protein replacement therapies. Due to the recent developments, the incorporation of modified nucleotides in synthetic mRNAs can lead to maximizing protein expression and reducing adverse immunogenicity. Despite these stunning improvements, mRNA therapy is limited by the need for the development of safe and efficient carriers to protect the mRNA integrity for in vivo applications. Recently, leading candidates for in vivo drug delivery vehicles are cell-derived exosomes, which have fewer immunogenic responses. In the current study, the key hurdles facing mRNA-based therapeutics, with an emphasis on recent strategies to overcoming its immunogenicity and instability, were highlighted. Then the immunogenicity and toxicity of exosomes derived from various cell sources were mentioned in detail. Finally, an overview of the recent strategies in using exosomes for mRNA delivery in the treatment of multiple diseases was stated.
在过去的十年中,治疗性信使 RNA(mRNA)作为一种极具前景的新型蛋白质替代疗法药物出现了。由于最近的发展,在合成 mRNA 中加入修饰核苷酸可以最大限度地提高蛋白质表达并降低免疫原性。尽管取得了这些惊人的进展,但 mRNA 疗法受到需要开发安全有效的载体以保护其完整性以用于体内应用的限制。最近,用于体内药物递送载体的主要候选物是细胞衍生的外泌体,其免疫原性反应较少。在当前的研究中,重点强调了基于 mRNA 的治疗方法所面临的关键障碍,以及克服其免疫原性和不稳定性的最新策略。然后详细介绍了来自各种细胞来源的外泌体的免疫原性和毒性。最后,概述了最近使用外泌体作为 mRNA 递送来治疗多种疾病的策略。