Publication: Optimization of Synthetic mRNA for Highly Efficient Translation and its Application in the Generation of Endothelial and Hematopoietic Cells from Human and Primate Pluripotent Stem Cells
Issued Date
2018-08-01
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ISSN
15586804
15508943
15508943
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2-s2.0-85043390738
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Mahidol University
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SCOPUS
Bibliographic Citation
Stem Cell Reviews and Reports. Vol.14, No.4 (2018), 525-534
Suggested Citation
Kran Suknuntha, Lihong Tao, Vera Brok-Volchanskaya, Saritha S. D’Souza, Akhilesh Kumar, Igor Slukvin Optimization of Synthetic mRNA for Highly Efficient Translation and its Application in the Generation of Endothelial and Hematopoietic Cells from Human and Primate Pluripotent Stem Cells. Stem Cell Reviews and Reports. Vol.14, No.4 (2018), 525-534. doi:10.1007/s12015-018-9805-1 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/45097
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Title
Optimization of Synthetic mRNA for Highly Efficient Translation and its Application in the Generation of Endothelial and Hematopoietic Cells from Human and Primate Pluripotent Stem Cells
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Abstract
© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Identification of transcription factors that directly convert pluripotent stem cells (PSCs) into endothelial and blood cells and advances in the chemical modifications of messenger RNA (mRNA) offer alternative nucleic acid-based transgene-free approach for scalable production of these cells for drug screening and therapeutic purposes. Here we evaluated the effect of 5′ and 3′ RNA untranslated regions (UTRs) on translational efficiency of chemically-modified synthetic mRNA (modRNA) in human PSCs and showed that an addition of 5′UTR indeed enhanced protein expression. With the optimized modRNAs expressing ETV2 or ETV2 and GATA2, we are able to produce VE-cadherin+ endothelial cells and CD34+CD43+ hematopoietic progenitors, respectively, from human PSCs as well as non-human primate (NHP) PSCs. Overall, our findings provide valuable information on the design of in vitro transcription templates being used in PSCs and its broad applicability for basic research, disease modeling, and regenerative medicine.