Bioengineering of noncoding RNAs for research agents and therapeutics.
Bioengineering of noncoding RNAs for research agents and therapeutics.
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DOI：
10.1002/wrna.1324
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发表时间：
2016-03
期刊：
影响因子：
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通讯作者：
Yu AM
中科院分区：
文献类型：
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作者：
Ho PY;Yu AM
功能性小非编码RNA（ncRNA）（如microRNA和小干扰RNA）在控制人类细胞过程中的发现为开发用于包括病毒感染和癌症在内的各种疾病的基于RNA的疗法开辟了新途径。然而，研究ncRNA功能和开发基于RNA的治疗方法依赖于获得大量负担得起的ncRNA试剂。目前，合成RNA占RNA研究和开发试剂的主要来源，但在核糖环和磷酸骨架上进行人工修饰，与细胞内产生的核碱基或未修饰的天然RNA分子上存在的转录后修饰形成鲜明对比。因此，近年来已经做出了大量努力来开发重组RNA技术以成本有效地生产可以更好地捕获天然RNA的结构、功能和安全性质的生物RNA试剂。在这篇文章中，我们总结和比较目前在体外和体内的方法生产的RNA剂，包括化学合成，体外转录，和生物工程的方法。我们强调了最新的重组RNA的方法，使用转移RNA（tRNA），核糖体RNA（rRNA），和最佳的ncRNA支架（OnRS），并讨论了生物工程ncRNA代理（BERA），应促进RNA的研究和开发的应用。
The discovery of functional small noncoding RNAs (ncRNAs), such as microRNAs and small interfering RNAs, in the control of human cellular processes has opened new avenues to develop RNA-based therapies for various diseases including viral infections and cancers. However, studying ncRNA functions and developing RNA-based therapeutics relies on access to large quantities of affordable ncRNA agents. Currently, synthetic RNAs account for the major source of agents for RNA research and development, yet carry artificial modifications on the ribose ring and phosphate backbone in sharp contrast to posttranscriptional modifications present on the nucleobases or unmodified natural RNA molecules produced within cells. Therefore, large efforts have been made in recent years to develop recombinant RNA techniques to cost-effectively produce biological RNA agents that may better capture the structure, function, and safety properties of natural RNAs. In this article, we summarize and compare current in vitro and in vivo methods for the production of RNA agents including chemical synthesis, in vitro transcription, and bioengineering approaches. We highlight the latest recombinant RNA approaches using transfer RNA (tRNA), ribosomal RNA (rRNA), and optimal ncRNA scaffold (OnRS), and discuss the applications of bioengineered ncRNA agents (BERAs) that should facilitate RNA research and development.