当前位置: X-MOL 学术Mol. Ther. Methods Clin. Dev. › 论文详情
Optimization of 5' Untranslated Region of Modified mRNA for Use in Cardiac or Hepatic Ischemic Injury.
Molecular Therapy - Methods & Clinical Development ( IF 4.875 ) Pub Date : 2020-03-31 , DOI: 10.1016/j.omtm.2020.03.019
Nishat Sultana,Yoav Hadas,Mohammad Tofael Kabir Sharkar,Keerat Kaur,Ajit Magadum,Ann Anu Kurian,Nadia Hossain,Bremy Alburquerque,Sakib Ahmed,Elena Chepurko,Lior Zangi

Modified mRNA (modRNA) is a gene-delivery platform for transiently introducing a single gene or several genes of interest to different cell types and tissues. modRNA is considered to be a safe vector for gene transfer, as it negligibly activates the innate immune system and does not compromise the genome integrity. The use of modRNA in basic and translational science is rising, due to the clinical potential of modRNA. We are currently using modRNA to induce cardiac regeneration post-ischemic injury. Major obstacles in using modRNA for cardiac ischemic disease include the need for the direct and single administration of modRNA to the heart and the inefficient translation of modRNA due to its short half-life. Modulation of the 5' untranslated region (5' UTR) to enhance translation efficiency in ischemic cardiac disease has great value, as it can reduce the amount of modRNA needed per delivery and will achieve higher and longer protein production post-single delivery. Here, we identified that 5' UTR, from the fatty acid metabolism gene carboxylesterase 1D (Ces1d), enhanced the translation of firefly luciferase (Luc) modRNA by 2-fold in the heart post-myocardial infarction (MI). Moreover, we identified, in the Ces1d, a specific RNA element (element D) that is responsible for the improvement of modRNA translation and leads to a 2.5-fold translation increment over Luc modRNA carrying artificial 5' UTR, post-MI. Importantly, we were able to show that 5' UTR Ces1d also enhances modRNA translation in the liver, but not in the kidney, post-ischemic injury, indicating that Ces1d 5' UTR and element D may play a wider role in translation of protein under an ischemic condition.
更新日期:2020-03-31

 

全部期刊列表>>
如何通过Nature平台传播科研成果
跟Nature、Science文章学绘图
隐藏1h前已浏览文章
课题组网站
新版X-MOL期刊搜索和高级搜索功能介绍
中洪博元
ACS材料视界
x-mol收录
南开大学
朱守非
廖良生
南方科技大学
西湖大学
伊利诺伊大学香槟分校
徐明华
中山大学化学工程与技术学院
试剂库存
天合科研
down
wechat
bug