Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), 123 St. Stephens Green, Dublin 2, Ireland.
Trinity Centre for Bioengineering, Trinity College Dublin (TCD), Dublin 2, Ireland.
Adv Healthc Mater. 2018 Jan;7(1). doi: 10.1002/adhm.201700695. Epub 2017 Oct 25.
microRNA-based therapies are an advantageous strategy with applications in both regenerative medicine (RM) and cancer treatments. microRNAs (miRNAs) are an evolutionary conserved class of small RNA molecules that modulate up to one third of the human nonprotein coding genome. Thus, synthetic miRNA activators and inhibitors hold immense potential to finely balance gene expression and reestablish tissue health. Ongoing industry-sponsored clinical trials inspire a new miRNA therapeutics era, but progress largely relies on the development of safe and efficient delivery systems. The emerging application of biomaterial scaffolds for this purpose offers spatiotemporal control and circumvents biological and mechanical barriers that impede successful miRNA delivery. The nascent research in scaffold-mediated miRNA therapies translates know-how learnt from studies in antitumoral and genetic disorders as well as work on plasmid (p)DNA/siRNA delivery to expand the miRNA therapies arena. In this progress report, the state of the art methods of regulating miRNAs are reviewed. Relevant miRNA delivery vectors and scaffold systems applied to-date for RM and cancer treatment applications are discussed, as well as the challenges involved in their design. Overall, this progress report demonstrates the opportunity that exists for the application of miRNA-activated scaffolds in the future of RM and cancer treatments.
基于 microRNA 的治疗策略是一种具有优势的策略，可应用于再生医学（RM）和癌症治疗。microRNAs（miRNAs）是一类进化上保守的小分子 RNA 分子，可调节人类非蛋白编码基因组的三分之一。因此，合成 miRNA 激活剂和抑制剂具有极大的潜力来精细平衡基因表达并恢复组织健康。正在进行的行业赞助的临床试验激发了 miRNA 治疗的新时代，但进展在很大程度上依赖于安全有效的递送系统的开发。生物材料支架在这方面的新兴应用提供了时空控制，并克服了阻碍成功 miRNA 递送的生物学和机械障碍。支架介导的 miRNA 治疗的新生研究将从抗肿瘤和遗传疾病研究以及质粒（p）DNA/siRNA 递送上的工作中学到的知识转化为扩大 miRNA 治疗领域。在本进展报告中，综述了调节 miRNAs 的最新方法。讨论了迄今为止应用于 RM 和癌症治疗应用的相关 miRNA 递送载体和支架系统，以及它们设计中涉及的挑战。总体而言，本进展报告表明，在未来的 RM 和癌症治疗中，应用 miRNA 激活支架具有很大的机会。
