RNA Therapeutics in Cardiovascular Precision Medicine.
RNA Therapeutics in Cardiovascular Precision Medicine.
复制标题
心血管精密医学中的RNA疗法。
DOI：
10.3389/fphys.2018.00953
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发表时间：
2018
影响因子：
4
通讯作者：
Stellos K
中科院分区：
文献类型：
--
作者：
Laina A;Gatsiou A;Georgiopoulos G;Stamatelopoulos K;Stellos K
由于我们对信使RNA（mRNA）的结构和功能的了解已经从仅仅是DNA和蛋白质之间的中间分子扩展到RNA是可以被修饰和编辑的动态基因调节剂的概念，RNA已经成为开发新的治疗方案的兴趣焦点。通过基于DNA和RNA的疗法对RNA分子的治疗性调节拓宽了感染性疾病、癌症、神经退行性疾病以及最近的心血管疾病中的治疗靶点的范围。目前，反义寡核苷酸（阿索）、小干扰RNA（siRNA）和microRNA是最广泛应用的靶向RNA分子并调节基因表达和蛋白质产生的治疗策略。然而，必须克服许多障碍，包括不稳定性、不充分的结合亲和力和向组织的递送、免疫原性和脱靶毒性，以便使这些药剂发展成有效的药物。由于心血管疾病仍然是全球死亡的主要原因，大量的临床试验正在开发中，研究RNA治疗剂在临床病症如家族性高胆固醇血症、糖尿病、高胆固醇血症、心脏淀粉样变性和心房纤颤中的安全性和功效。本文综述了RNA靶向治疗在心血管疾病中的临床试验，并重点讨论了RNA靶向治疗在精确转录医学中的进展、结果、局限性和未来发展方向。
Since our knowledge on structure and function of messenger RNA (mRNA) has expanded from merely being an intermediate molecule between DNA and proteins to the notion that RNA is a dynamic gene regulator that can be modified and edited, RNA has become a focus of interest into developing novel therapeutic schemes. Therapeutic modulation of RNA molecules by DNA- and RNA-based therapies has broadened the scope of therapeutic targets in infectious diseases, cancer, neurodegenerative diseases and most recently in cardiovascular diseases as well. Currently, antisense oligonucleotides (ASO), small interfering RNAs (siRNAs), and microRNAs are the most widely applied therapeutic strategies to target RNA molecules and regulate gene expression and protein production. However, a number of barriers have to be overcome including instability, inadequate binding affinity and delivery to the tissues, immunogenicity, and off-target toxicity in order for these agents to evolve into efficient drugs. As cardiovascular diseases remain the leading cause of mortality worldwide, a large number of clinical trials are under development investigating the safety and efficacy of RNA therapeutics in clinical conditions such as familial hypercholesterolemia, diabetes mellitus, hypertriglyceridemia, cardiac amyloidosis, and atrial fibrillation. In this review, we summarize the clinical trials of RNA-targeting therapies in cardiovascular disease and critically discuss the advances, the outcomes, the limitations and the future directions of RNA therapeutics in precision transcriptomic medicine.
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DOI：
10.1126/science.aaf5573
发表时间：
2016-08-05
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Abudayyeh OO;Gootenberg JS;Konermann S;Joung J;Slaymaker IM;Cox DB;Shmakov S;Makarova KS;Semenova E;Minakhin L;Severinov K;Regev A;Lander ES;Koonin EV;Zhang F
通讯作者：
Zhang F
影响因子：
24
作者：
Capoulade, Romain;Chan, Kwan L.;Tsimikas, Sotirios
通讯作者：
Tsimikas, Sotirios
DOI：
10.1073/pnas.1206432109
发表时间：
2012-10-23
影响因子：
11.1
作者：
Bernardo, Bianca C.;Gao, Xiao-Ming;McMullen, Julie R.
通讯作者：
McMullen, Julie R.
影响因子：
--
作者：
Bennet, Anna;Di Angelantonio, Ernanuele;Gudnason, Vilmundur
通讯作者：
Gudnason, Vilmundur
影响因子：
39.3
作者：
Dernellis, J;Panaretou, M
通讯作者：
Panaretou, M