» Articles » PMID: 30598301

MRNA-Based Genetic Reprogramming

Overview
Journal Mol Ther
Publisher Cell Press
Date 2019 Jan 2
PMID 30598301
Citations 44
Authors
Affiliations
Soon will be listed here.
Abstract

The discovery that ordinary skin cells can be turned into pluripotent stem cells by the forced expression of defined factors has raised hopes that personalized regenerative treatments based on immunologically compatible material derived from a patient's own cells might be realized in the not-too-distant future. A major barrier to the clinical use of induced pluripotent stem cells (iPSCs) was initially presented by the need to employ integrating viral vectors to express the factors that induce an embryonic gene expression profile, which entails potentially oncogenic alteration of the normal genome. Several "non-integrating" reprogramming systems have been developed over the last decade to address this problem. Among these techniques, mRNA reprogramming is the most unambiguously "footprint-free," most productive, and perhaps the best suited to clinical production of stem cells. Herein, we discuss the origins of the mRNA-based reprogramming system, its benefits and drawbacks, recent technical improvements that simplify its application, and the status of current efforts to industrialize this approach to mass-produce human stem cells for the clinic.

Citing Articles

UTR-Insight: integrating deep learning for efficient 5' UTR discovery and design.

Pan S, Wang H, Zhang H, Tang Z, Xu L, Yan Z BMC Genomics. 2025; 26(1):107.

PMID: 39905334 PMC: 11796101. DOI: 10.1186/s12864-025-11269-7.


Engineered biomaterials in stem cell-based regenerative medicine.

Zhu F, Nie G, Liu C Life Med. 2025; 2(4):lnad027.

PMID: 39872549 PMC: 11749850. DOI: 10.1093/lifemedi/lnad027.


Combining the induced pluripotent stem cell (iPSC) technology with chimeric antigen receptor (CAR)-based immunotherapy: recent advances, challenges, and future prospects.

Alidadi M, Barzgar H, Zaman M, Paevskaya O, Metanat Y, Khodabandehloo E Front Cell Dev Biol. 2024; 12:1491282.

PMID: 39624236 PMC: 11609223. DOI: 10.3389/fcell.2024.1491282.


The Role of Human-Induced Pluripotent Stem Cells in Studying Cardiac Channelopathies.

Begovic M, Schneider L, Zhou X, Hamdani N, Akin I, El-Battrawy I Int J Mol Sci. 2024; 25(22).

PMID: 39596103 PMC: 11593457. DOI: 10.3390/ijms252212034.


Bridging the gap: a translational perspective in spinal cord injury.

Hassan O, Takamiya S, Asgarihafshejani A, Fehlings M Exp Biol Med (Maywood). 2024; 249:10266.

PMID: 39391076 PMC: 11464315. DOI: 10.3389/ebm.2024.10266.


References
1.
El-Sayed A, Zhang Z, Zhang L, Liu Z, Abbott L, Zhang Y . Pluripotent state induction in mouse embryonic fibroblast using mRNAs of reprogramming factors. Int J Mol Sci. 2014; 15(12):21840-64. PMC: 4284681. DOI: 10.3390/ijms151221840. View

2.
Van Tendeloo V, Ponsaerts P, Lardon F, Nijs G, Lenjou M, Van Broeckhoven C . Highly efficient gene delivery by mRNA electroporation in human hematopoietic cells: superiority to lipofection and passive pulsing of mRNA and to electroporation of plasmid cDNA for tumor antigen loading of dendritic cells. Blood. 2001; 98(1):49-56. DOI: 10.1182/blood.v98.1.49. View

3.
Yu J, Hu K, Smuga-Otto K, Tian S, Stewart R, Slukvin I . Human induced pluripotent stem cells free of vector and transgene sequences. Science. 2009; 324(5928):797-801. PMC: 2758053. DOI: 10.1126/science.1172482. View

4.
Yoshida Y, Takahashi K, Okita K, Ichisaka T, Yamanaka S . Hypoxia enhances the generation of induced pluripotent stem cells. Cell Stem Cell. 2009; 5(3):237-41. DOI: 10.1016/j.stem.2009.08.001. View

5.
Steichen C, Luce E, Maluenda J, Tosca L, Moreno-Gimeno I, Desterke C . Messenger RNA- versus retrovirus-based induced pluripotent stem cell reprogramming strategies: analysis of genomic integrity. Stem Cells Transl Med. 2014; 3(6):686-91. PMC: 4039453. DOI: 10.5966/sctm.2013-0158. View