As the central template for protein expression,messenger ribonucleic acid(mRNA)holds immense potential for novel therapeutic strategies.Over the past few decades,mRNA-based therapeutics have demonstrated remarkable ef...As the central template for protein expression,messenger ribonucleic acid(mRNA)holds immense potential for novel therapeutic strategies.Over the past few decades,mRNA-based therapeutics have demonstrated remarkable efficacy in a range of applications,including epidemic vaccine,cancer vaccine,protein replacement therapy,cytokine therapy,cell therapy and gene editing.Due to the inherent instability of mRNA,the rational design of mRNA structure is the prerequisite for therapeutic utility while effective delivery systems are also essential for in vivo applications.This review focuses on the optimization of mRNA structure and highlights key delivery strategies.It also provides a comprehensive overview of the major applications of mRNA-based strategies.In addition,it highlights the persistent challenges in m RNA therapeutics,particularly in terms of stability,immunogenicity,delivery efficiency and safety.By examining recent advances in mRNA design,delivery and application,this review aims to support ongoing research and development in the field of mRNA-based therapeutics.展开更多
Analysis of the secondary structures of mRNAs which encode mature peptides shows that the location of each codon in mRNA secondary structure has a trend, which appears to be in agreement with the conformational proper...Analysis of the secondary structures of mRNAs which encode mature peptides shows that the location of each codon in mRNA secondary structure has a trend, which appears to be in agreement with the conformational property of the corresponding amino acid to some extent. Most of the codons that encode hydrophobic amino acids are located in stable stem regions of mRNA secondary structures, and vice versa, most of the codons that encode hydrophilic amino acids are located in flexible loop regions. This result supports the recent conclusion that there may be the information transfer between the three dimensional structures of mRNA and the encoded protein.展开更多
As more information is gathered on the mechanisms of transcription and translation, it is becoming apparent that these processes are highly regulated. The formation of mRNA secondary and tertiary structures is one suc...As more information is gathered on the mechanisms of transcription and translation, it is becoming apparent that these processes are highly regulated. The formation of mRNA secondary and tertiary structures is one such regulatory process that until recently it has not been analysed in depth. Formation of these mRNA structures has the potential to enhance and inhibit alternative splicing of transcripts, and regulate rates and amount of translation. As this regulatory mechanism potentially impacts at both the transcriptional and translational level, while also potentially utilising the vast array of non-coding RNAs, it warrants further investigation. Currently, a variety of high- throughput sequencing techniques including parallel analysis of RNA structure （PARS）, fragmentation sequencing （FragSeq） and selective 2-hydroxyl acylation analysed by primer extension （SHAPE） lead the way in the genome-wide identification and analysis of mRNA structure formation. These new sequencing techniques highlight the diversity and complexity of the transcriptome, and demonstrate another regulatory mechanism that could become a target for new therapeutic approaches.展开更多
For a long time,mutations that do not alter protein sequences,so-called synonymous mutations,were largely overlooked.Scientists assumed they had little to no biological impact,considering them as neutral background no...For a long time,mutations that do not alter protein sequences,so-called synonymous mutations,were largely overlooked.Scientists assumed they had little to no biological impact,considering them as neutral background noise in the course of evolution.But a new study by Xin et al.(2025)challenges that assumption.Their research reveals that one such"silent"mutation played a pivotal role in cucumber domestication(Che and Zhang,2019).Rather than being inert,the mutation triggered a cascade of molecular changes involving mRNA structure and chemical modifications,ultimately altering hormone levels and growth patterns.These findings mark a turning point in our understanding of gene regulation,exposing RNA,not just DNA or protein,as a major driver of evolutionary change.展开更多
基金supported by the National Key Research and Development Program of China(No.2023YFA0915400)the National Natural Science Foundation of China(No.22277072,22407099 and 32401161)+3 种基金Shanghai Oriental Talents(QNWS2024055)Shanghai Municipal Science and Technology Commission(No.24ZR1462700)the Science and Technology Development Fund of Pudong Health Bureau of Shanghai(No.PKJ2024-Y40)“Clinic Plus”Outstanding Project(No.2021ZYB009 and No.2021ZYB003)from Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine,and Innovative research team of high-level local universities in Shanghai。
文摘As the central template for protein expression,messenger ribonucleic acid(mRNA)holds immense potential for novel therapeutic strategies.Over the past few decades,mRNA-based therapeutics have demonstrated remarkable efficacy in a range of applications,including epidemic vaccine,cancer vaccine,protein replacement therapy,cytokine therapy,cell therapy and gene editing.Due to the inherent instability of mRNA,the rational design of mRNA structure is the prerequisite for therapeutic utility while effective delivery systems are also essential for in vivo applications.This review focuses on the optimization of mRNA structure and highlights key delivery strategies.It also provides a comprehensive overview of the major applications of mRNA-based strategies.In addition,it highlights the persistent challenges in m RNA therapeutics,particularly in terms of stability,immunogenicity,delivery efficiency and safety.By examining recent advances in mRNA design,delivery and application,this review aims to support ongoing research and development in the field of mRNA-based therapeutics.
文摘Analysis of the secondary structures of mRNAs which encode mature peptides shows that the location of each codon in mRNA secondary structure has a trend, which appears to be in agreement with the conformational property of the corresponding amino acid to some extent. Most of the codons that encode hydrophobic amino acids are located in stable stem regions of mRNA secondary structures, and vice versa, most of the codons that encode hydrophilic amino acids are located in flexible loop regions. This result supports the recent conclusion that there may be the information transfer between the three dimensional structures of mRNA and the encoded protein.
文摘As more information is gathered on the mechanisms of transcription and translation, it is becoming apparent that these processes are highly regulated. The formation of mRNA secondary and tertiary structures is one such regulatory process that until recently it has not been analysed in depth. Formation of these mRNA structures has the potential to enhance and inhibit alternative splicing of transcripts, and regulate rates and amount of translation. As this regulatory mechanism potentially impacts at both the transcriptional and translational level, while also potentially utilising the vast array of non-coding RNAs, it warrants further investigation. Currently, a variety of high- throughput sequencing techniques including parallel analysis of RNA structure （PARS）, fragmentation sequencing （FragSeq） and selective 2-hydroxyl acylation analysed by primer extension （SHAPE） lead the way in the genome-wide identification and analysis of mRNA structure formation. These new sequencing techniques highlight the diversity and complexity of the transcriptome, and demonstrate another regulatory mechanism that could become a target for new therapeutic approaches.
基金A.Bendahmane and A.Boualem are supported by Saclay Plant Sciences(SPS)(ANR-17-EUR-0007)the NectarGland ERC Project(101095736)+1 种基金Explor'ae ANR-24-RRll-0003the Plant Biology and Breeding Department of INRAE.
文摘For a long time,mutations that do not alter protein sequences,so-called synonymous mutations,were largely overlooked.Scientists assumed they had little to no biological impact,considering them as neutral background noise in the course of evolution.But a new study by Xin et al.(2025)challenges that assumption.Their research reveals that one such"silent"mutation played a pivotal role in cucumber domestication(Che and Zhang,2019).Rather than being inert,the mutation triggered a cascade of molecular changes involving mRNA structure and chemical modifications,ultimately altering hormone levels and growth patterns.These findings mark a turning point in our understanding of gene regulation,exposing RNA,not just DNA or protein,as a major driver of evolutionary change.
