IBE, MERLN Institute for Technology - Inspired Regenerative Medicine, Maastricht University, Maastricht, The Netherlands; Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, MN, USA.
Curr Opin Biotechnol. 2022 Apr;74:8-14. doi: 10.1016/j.copbio.2021.10.015. Epub 2021 Nov 5.
mRNA has the potential to be the next generation drug for tissue restoration in regenerative medicine. The variety of mRNAs that could be synthesized with the aim of increasing the expression of any required protein offers new opportunities. However, the intrinsic immunogenicity and lack of stability of mRNA has long restricted the potential of mRNA therapeutics. Fortunately, considerable progress has been made on synthetic mRNA modifications and relevant purification steps that have overcome these limitations. However, there remains a lack of efficient mRNA delivery strategies. Additionally, mRNA may need to be administered in situ via three-dimensional biomaterials. These materials, also known as transcript-activated matrices, require further consideration in terms of mRNA loading and release, immunogenicity, and other features. In this article, various limiting factors in mRNA synthesis, vector formulation, and local delivery to tissues are highlighted together with current developments and the future outlook for mRNA therapeutics in tissue regeneration.
mRNA 有可能成为再生医学中组织修复的下一代药物。通过合成各种 mRNAs 来提高任何所需蛋白质的表达水平，这提供了新的机会。然而，mRNA 的固有免疫原性和缺乏稳定性长期以来限制了 mRNA 疗法的潜力。幸运的是，在合成 mRNA 修饰和相关纯化步骤方面已经取得了相当大的进展，这些进展克服了这些限制。然而，仍然缺乏有效的 mRNA 传递策略。此外，mRNA 可能需要通过三维生物材料原位给药。这些材料也称为转录激活基质，在 mRNA 加载和释放、免疫原性和其他特性方面需要进一步考虑。本文重点介绍了 mRNA 合成、载体配方和局部递送至组织中的各种限制因素，以及当前的发展和 mRNA 疗法在组织再生中的未来前景。
