Application of Modified mRNA in Somatic Reprogramming to Pluripotency and Directed Conversion of Cell Fate

Wang, Aline Yen Ling

doi:10.3390/ijms22158148

Cited by 20 publications

(18 citation statements)

References 128 publications

(234 reference statements)

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“… 21 However, reprogramming using synthetic modified mRNAs requires serial transgene delivery, and blood cells seem to be difficult for reprogramming using the modified mRNA technology. 22 The co-delivery of microRNA-302s/367 with synthetic modified mRNAs into fibroblasts promoted the generation of iPSCs with a high efficiency, 23 which might be tested in blood cells.…”

Section: Somatic Origin Of Human Ipscs and Reprogramming Methodsmentioning

confidence: 99%

Human Induced Pluripotent Stem Cells: From Cell Origin, Genomic Stability, and Epigenetic Memory to Translational Medicine

2022

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The potential of human induced pluripotent stem cells (iPSCs) to self-renew indefinitely and to differentiate virtually into any cell type in unlimited quantities makes them attractive for in-vitro disease modeling, drug screening, personalized medicine, and regenerative therapies. As the genome of iPSCs thoroughly reproduces that of the somatic cells from which they are derived, they may possess genetic abnormalities, which would seriously compromise their utility and safety. Genetic aberrations could be present in donor somatic cells and then transferred during iPSC generation, or they could occur as de novo mutations during reprogramming or prolonged cell culture. Therefore, to warrant safety of human iPSCs for clinical applications, analysis of genetic integrity, particularly during iPSC generation and differentiation, should be carried out on a regular basis. On the other hand, reprogramming of somatic cells to iPSCs requires profound modifications in the epigenetic landscape. Changes in chromatin structure by DNA methylations and histone tail modifications aim to reset the gene expression pattern of somatic cells to facilitate and establish self-renewal and pluripotency. However, residual epigenetic memory influences the iPSC phenotype, which may affect their application in disease therapeutics. The present review discusses the somatic cell origin, genetic stability, and epigenetic memory of iPSCs and their impact on basic and translational research.

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Section: Somatic Origin Of Human Ipscs and Reprogramming Methodsmentioning

confidence: 99%

Human Induced Pluripotent Stem Cells: From Cell Origin, Genomic Stability, and Epigenetic Memory to Translational Medicine

2022

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“…Recently, substantial modifications of mRNA have been investigated for their extensive applications. A modRNA-based vaccine contains 5′ cap, 5′ UTR (untranslated region), 3′ UTR, poly-A tail, and open reading frame (ORF) 79 , 80 . modRNA can be fully transcribed in vitro from a linearized DNA plasmid template by the enzymatic reaction in a cell-free system 81 , 82 .…”

Section: Covid-19 Modrna Vaccinesmentioning

confidence: 99%

“…The plasmid acts as a DNA template that transcripts an mRNA using an RNA polymerase in in vitro transcription (IVT). Subsequently, DNase is added to degrade the plasmid template and a novel cap analog 83 – 85 . As natural 5′ cap, including m7G, competes with guanosine triphosphate (GTP), it risks uncapping or becoming inactive mRNA.…”

Section: Covid-19 Modrna Vaccinesmentioning

confidence: 99%

“…New cap analogs (P(1)-3′-O,7-dimethylguanosine-5′ P3-guanosine-5′ triphosphate) were designed, named antireverse cap analogs (ARCAs), that are not able to incorporate in the reverse orientation and skip degeneration by Dcp2 (mRNA-decaying enzymes) 83 . The incorporation of a cap analog can enhance translation efficiency and modRNA stability 65 , 83 , 87 – 89 . Substantial modification in mRNA was reported 90 , whereas only a small subset of modified nucleotides, such as 5-methylcytidine, pseudouridine, 5-methyluridine, N6-methyladenosine, N1-methyl-pseudouridine, and 5-methoxyuridine, were demonstrated to enhance translation efficiency and mRNA stability 65 , 77 , 88 , 91 – 93 .…”

Section: Covid-19 Modrna Vaccinesmentioning

confidence: 99%

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Modified mRNA-Based Vaccines Against Coronavirus Disease 2019

Wang

2022

Cell Transplant

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The pandemic of coronavirus disease 2019 (COVID-19) continuously causes deaths worldwide, representing a considerable challenge to health care and economic systems with a new precedent in human history. Many therapeutic medicines primarily focused on preventing severe organ damage and complications, which can be fatal in some confirmed cases. The synthesized modified mRNA (modRNA) represents a nonviral, integration-free, zero-footprint, efficient, and safe strategy for vaccine discovery. modRNA-based technology has facilitated the rapid development of the first COVID-19 vaccines due to its cost- and time-saving properties, thus initiating a new era of prophylactic vaccines against infectious diseases. Recently, COVID-19 modRNA vaccines were approved, and a large-scale vaccination campaign began worldwide. To date, results suggest that the modRNA vaccines are highly effective against virus infection, which causes COVID-19. Although short-term studies have reported that their safety is acceptable, long-term safety and protective immunity remain unclear. In this review, we describe two major approved modRNA vaccines and discuss their potential myocarditis complications.

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“…These cells are similar to ESCs in characteristics such as morphology, pluripotency, and marker expression. While ESCs are obtained from the blastocyst᾽s inner cell mass (ICM), iPSCs can be derived from a wide range of different cellular sources using different reprogramming methods ( Wang, 2021 ). In the earliest studies on iPSCs, the Yamanaka laboratory used different types of retroviruses to produce iPSCs, each carrying only one type of the transcription factor.…”

Section: Introductionmentioning

confidence: 99%

Induced pluripotent stem cells: Generation methods and a new perspective in COVID-19 research

Karami

Moradi

Eidi

et al. 2023

Front. Cell Dev. Biol.

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Induced pluripotent stem cells (iPSCs) exhibit an unlimited ability to self-renew and produce various differentiated cell types, thereby creating high hopes for both scientists and patients as a great tool for basic research as well as for regenerative medicine purposes. The availability and safety of iPSCs for therapeutic purposes require safe and highly efficient methods for production of these cells. Different methods have been used to produce iPSCs, each of which has advantages and disadvantages. Studying these methods would be very helpful in developing an easy, safe, and efficient method for the generation of iPSCs. Since iPSCs can be generated from somatic cells, they can be considered as valuable cellular resources available for important research needs and various therapeutic purposes. Coronavirus disease 2019 (COVID-19) is a disease that has endangered numerous human lives worldwide and currently has no definitive cure. Therefore, researchers have been rigorously studying and examining all aspects of COVID-19 and potential treatment modalities and various drugs in order to enable the treatment, control, and prevention of COVID-19. iPSCs have become one of the most attractive and promising tools in this field by providing the ability to study COVID-19 and the effectiveness of drugs on this disease outside the human body. In this study, we discuss the different methods of generation of iPSCs as well as their respective advantages and disadvantages. We also present recent applications of iPSCs in the study and treatment of COVID-19.

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Application of Modified mRNA in Somatic Reprogramming to Pluripotency and Directed Conversion of Cell Fate

Cited by 20 publications

References 128 publications

Human Induced Pluripotent Stem Cells: From Cell Origin, Genomic Stability, and Epigenetic Memory to Translational Medicine

Human Induced Pluripotent Stem Cells: From Cell Origin, Genomic Stability, and Epigenetic Memory to Translational Medicine

Modified mRNA-Based Vaccines Against Coronavirus Disease 2019

Induced pluripotent stem cells: Generation methods and a new perspective in COVID-19 research

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