3′-Modification stabilizes mRNA and increases translation in cells

Gampe, Christian M.; White, Amy C. Seila; Siva, Swetha; Zécri, Frédéric; Diener, John L

doi:10.1016/j.bmcl.2018.06.008

Cited by 9 publications

(8 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During eukaryotic mRNA degradation, deadenylation by 3 0 -exonucleases such as the poly(A)-specific ribonuclease (PARN) selectively deadenylates single-stranded mRNA via recognition of the 2 0 ,3 0 -adenosine diol intermediate [89]. Chemical modification of the end 2 0 ,3 0 -diol group in a synthetic Luciferase mRNA resulted in a threefold increase in protein synthesis due to an increase in transcript stability [90]. These findings suggest that chemical modification of the mRNA's 3 0 end might interfere with the cellular interactions that lead to decay.…”

Section: Modifications Of the Mrna Terminimentioning

confidence: 99%

Effects of mRNA Modifications on Translation: An Overview

Roy

2021

Methods in Molecular Biology

View full text Add to dashboard Cite

The mRNA epitranscriptome imparts diversity to gene expression by installing chemical modifications. Advances in detection methods have identified chemical modifications in eukaryotic, bacterial, and viral messenger RNAs (mRNAs). The biological functions of modifications in mRNAs still remain to be understood. Chemical modifications are introduced in synthetic mRNAs meant for therapeutic applications to maximize expression from the synthetic mRNAs and to evade the host immune response. This overview provides a background of chemical modifications found in mRNAs, with an emphasis on pseudouridine and its known effects on the mRNA life cycle, its potential applications in synthetic mRNA, and the methods used to assess its effects on mRNA translation.

show abstract

Section: Modifications Of the Mrna Terminimentioning

confidence: 99%

Effects of mRNA Modifications on Translation: An Overview

Roy

2021

Methods in Molecular Biology

View full text Add to dashboard Cite

show abstract

“…74 Similarly, mRNA is quickly degraded upon delivery; one study using LNPs to deliver Cas9 mRNA and single-guide (sg)RNA found that within a few hours the vast majority of delivered RNA had been degraded. 75 As with siRNAs, it may be possible to incorporate site-specific structural modifications into mRNA to improve stability and prolong expression; examples include chemical modifications to the 3 0 end, 76 incorporation of sugar-modified bases into the poly(A) tail, 77 and circularization of mRNA. 72…”

Section: Reviewmentioning

confidence: 99%

Nanoscale delivery platforms for RNA therapeutics: Challenges and the current state of the art

Rhym

Anderson

2022

Med

View full text Add to dashboard Cite

“…Most of these tail modifications stay at the last 3’-end of synthetic mRNA and can significantly reduce the possibility of mRNA degradation by 3’-to-5’ exonucleases. As a result, synthetic mRNA is endowed with a lengthened half-life and an increased translation efficiency in vitro and in vivo [51] , [52] , [53] . The fluorophore-labeled mRNA can be visualized during its metabolic lifecycle [53] .…”

Section: Chemical Modifications Of Synthetic Mrnamentioning

confidence: 99%

“…As a result, synthetic mRNA is endowed with a lengthened half-life and an increased translation efficiency in vitro and in vivo [51] , [52] , [53] . The fluorophore-labeled mRNA can be visualized during its metabolic lifecycle [53] . Of note, there are also other strategies to improve the translation and stability of IVT mRNA inside cells such as introduction of stabilizing elements [ 54 , 55 ], secondary structure [56] , high GC content [57] , and optimized codon [ 58 , 59 ], but these contents are not the focus of this review.…”

Section: Chemical Modifications Of Synthetic Mrnamentioning

confidence: 99%

Synthetic modified messenger RNA for therapeutic applications

et al. 2021

View full text Add to dashboard Cite

Synthetic modified messenger RNA (mRNA) has manifested great potentials for therapeutic applications such as vaccines and gene therapies, with the recent mRNA vaccines for global pandemic COVID-19 (corona virus disease 2019) attracting the tremendous attention. The chemical modifications and delivery vehicles of synthetic mRNAs are the two key factors for their in vivo therapeutic applications. Chemical modifications like nucleoside methylation endow the synthetic mRNAs with high stability and reduced stimulation of innate immunity. The development of scalable production of synthetic mRNA and efficient mRNA formulation and delivery strategies in recent years have remarkably advanced the field. It is worth noticing that we had limited knowledge on the roles of mRNA modifications in the past. However, the last decade has witnessed not only new discoveries of several naturally occurring mRNA modifications but also substantial advances in understanding their roles on regulating gene expression. It is highly necessary to reconsider the therapeutic system made by synthetic modified mRNAs and delivery vectors. In this review, we will mainly discuss the roles of various chemical modifications on synthetic mRNAs, briefly summarize the progresses of mRNA delivery strategies, and highlight some latest mRNA therapeutics applications including infectious disease vaccines, cancer immunotherapy, mRNA-based genetic reprogramming and protein replacement, mRNA-based gene editing.

show abstract

3′-Modification stabilizes mRNA and increases translation in cells

Cited by 9 publications

References 20 publications

Effects of mRNA Modifications on Translation: An Overview

Effects of mRNA Modifications on Translation: An Overview

Nanoscale delivery platforms for RNA therapeutics: Challenges and the current state of the art

Synthetic modified messenger RNA for therapeutic applications

Contact Info

Product

Resources

About