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
Bone fractures represent a significant global healthcare burden.Although fractures typically heal on their own,some fail to regenerate properly,leading to nonunion,a condition that causes prolonged disability,morbidit...Bone fractures represent a significant global healthcare burden.Although fractures typically heal on their own,some fail to regenerate properly,leading to nonunion,a condition that causes prolonged disability,morbidity,and mortality.The challenge of treating nonunion fractures is further complicated in patients with underlying bone disorders where systemic and local factors impair bone healing.Traditional treatment approaches,including autografts,allografts,xenografts,and synthetic biomaterials,face limitations such as donor site pain,immune rejection,and insufficient mechanical strength,underscoring the need for alternative strategies.Biologic therapies have emerged as promising tools to enhance bone regeneration by leveraging the body’s natural healing processes.This review explores the critical role of conventional and emerging biologics in fracture healing.We categorize biologic therapies into protein-based treatments,gene and transcript therapies,small molecules,peptides,and cell-based therapies,highlighting their mechanisms of action,advantages,and clinical relevance.Finally,we examine the potential applications of biologics in treating fractures associated with bone disorders such as osteoporosis,osteogenesis imperfecta,rickets,osteomalacia,Paget’s disease,and bone tumors.By integrating biologic therapies with existing biomaterial-based strategies,these innovative approaches have the potential to transform clinical management and improve outcomes for patients with difficult-to-heal fractures.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.
基金performed as part of the cmRNAbone project funded by the European Union’s Horizon 2020 research and innovation program under the Grant Agreement No 874790。
文摘Bone fractures represent a significant global healthcare burden.Although fractures typically heal on their own,some fail to regenerate properly,leading to nonunion,a condition that causes prolonged disability,morbidity,and mortality.The challenge of treating nonunion fractures is further complicated in patients with underlying bone disorders where systemic and local factors impair bone healing.Traditional treatment approaches,including autografts,allografts,xenografts,and synthetic biomaterials,face limitations such as donor site pain,immune rejection,and insufficient mechanical strength,underscoring the need for alternative strategies.Biologic therapies have emerged as promising tools to enhance bone regeneration by leveraging the body’s natural healing processes.This review explores the critical role of conventional and emerging biologics in fracture healing.We categorize biologic therapies into protein-based treatments,gene and transcript therapies,small molecules,peptides,and cell-based therapies,highlighting their mechanisms of action,advantages,and clinical relevance.Finally,we examine the potential applications of biologics in treating fractures associated with bone disorders such as osteoporosis,osteogenesis imperfecta,rickets,osteomalacia,Paget’s disease,and bone tumors.By integrating biologic therapies with existing biomaterial-based strategies,these innovative approaches have the potential to transform clinical management and improve outcomes for patients with difficult-to-heal fractures.
