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
Open accessAbstract
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.
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Opportunities and Challenges in the Delivery of mRNA-Based Vaccines
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- Authors
- Suknuntha, K., Tao, L., Brok-Volchanskaya, V., D’Souza, S. S., Kumar, A., & Slukvin, I.
- Affiliations
- University of Wisconsin–Madison (US)
- University of Wisconsin System (US)
- Corresponding author
- Suknuntha, Kran
- Venue
- Stem Cell Reviews and Reports
- Published
- 2018-03-08
- Volume
- 14
- Issue
- 4
- Pages
- 525-534
- ISSN
- 1550-8943 (ISSN-L)
- 1558-6804
- PMC
- PMC6014909
- OpenAlex
- W2790531361
- Cited by
- 35
- References
- 4
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 9 · 2021: 2 · 2020: 6 · 2019: 3 · 2018: 1
- FWCI
- 1.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Stem Cell Reviews and Reports (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL132891)
- National Institute of General Medical Sciences (P51 RR000167)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- synthetic mRNA, chemically modified mRNA, translation efficiency, pluripotent stem cells, endothelial differentiation, hematopoietic progenitor cells, ETV2, GATA2, disease modeling, regenerative medicine
- MeSH terms
- Cadherin 5, Animals, Cell Differentiation, Cell Line, Cells, Cultured, Hematopoietic Stem Cells, Humans, Primates, RNA, Messenger, Transcription Factors, Protein Biosynthesis, Antigens, CD, Cadherins, Antigens, CD34, 5' Untranslated Regions, Pluripotent Stem Cells, Endothelial Cells, GATA2 Transcription Factor, Leukosialin
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