About: Optimization of 5′ Untranslated Region of Modified mRNA for Use in Cardiac or Hepatic Ischemic Injury

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About: Optimization of 5′ Untranslated Region of Modified mRNA for Use in Cardiac or Hepatic Ischemic Injury Goto Sponge NotDistinct Permalink

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Optimization of 5′ Untranslated Region of Modified mRNA for Use in Cardiac or Hepatic Ischemic Injury
Creator	Ahmed, Sakib Alburquerque, Bremy Chepurko, Elena Hadas, Yoav Hossain, Nadia Kaur, Keerat Kurian, Ann Magadum, Ajit Sharkar, Kabir Sultana, Nishat Tofael, Mohammad Zangi, Lior
Source	PMC
abstract	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.
has issue date	2020-03-31(xsd:dateTime)
bibo:doi	10.1016/j.omtm.2020.03.019
bibo:pmid	32300609
has license	cc-by
sha1sum (hex)	405b7718d791bd847e96ddbdf42dab4595ec58f2
schema:url	https://doi.org/10.1016/j.omtm.2020.03.019
resource representing a document's title	Optimization of 5′ Untranslated Region of Modified mRNA for Use in Cardiac or Hepatic Ischemic Injury
has PubMed Central identifier	PMC7150433
has PubMed identifier	32300609
schema:publication	Mol Ther Methods Clin Dev
resource representing a document's body	covid:405b7718d791bd847e96ddbdf42dab4595ec58f2#body_text
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