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
目的:研究五虎汤对病毒诱发幼年哮喘大鼠脾细胞悬液T-bet、GATA-3、RORγt、Foxp3 m RNA表达的影响。方法:采用RSV诱导OVA致敏大鼠哮喘模型。造模成功后,随机分成五虎汤高、中、低[4.752 g/(kg·d)、2.376 g/(kg·d)、1.188 g/(...目的:研究五虎汤对病毒诱发幼年哮喘大鼠脾细胞悬液T-bet、GATA-3、RORγt、Foxp3 m RNA表达的影响。方法:采用RSV诱导OVA致敏大鼠哮喘模型。造模成功后,随机分成五虎汤高、中、低[4.752 g/(kg·d)、2.376 g/(kg·d)、1.188 g/(kg·d)]剂量组、地塞米松组[地塞米松片,2.4 mg/(kg·d))]、模型组。干预14 d后,取脾组织,采用RT-PCR法检测脾细胞悬液中T-bet、GATA-3、RORγt、Foxp3 m RNA表达情况。结果:模型组脾组织T-bet、Foxp3m RNA表达低于空白组(P<0.05),而GATA-3、RORγt m RNA表达高于空白对照组(P<0.05)。五虎汤高、中剂量组脾组织GATA-3、RORγt m RNA表达均明显低于模型组(P<0.01或P<0.05),而T-bet、Foxp3 m RNA表达均明显高于模型组(P<0.01或P<0.05)。结论:五虎汤能调控病毒诱发幼年哮喘大鼠脾组织转录因子T-bet、GATA-3、RORγt、Foxp3 m RNA的表达,调控Thl、Th2、Thl7、Treg细胞,重建免疫平衡,抑制哮喘气道炎症形成。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.
文摘目的:研究五虎汤对病毒诱发幼年哮喘大鼠脾细胞悬液T-bet、GATA-3、RORγt、Foxp3 m RNA表达的影响。方法:采用RSV诱导OVA致敏大鼠哮喘模型。造模成功后,随机分成五虎汤高、中、低[4.752 g/(kg·d)、2.376 g/(kg·d)、1.188 g/(kg·d)]剂量组、地塞米松组[地塞米松片,2.4 mg/(kg·d))]、模型组。干预14 d后,取脾组织,采用RT-PCR法检测脾细胞悬液中T-bet、GATA-3、RORγt、Foxp3 m RNA表达情况。结果:模型组脾组织T-bet、Foxp3m RNA表达低于空白组(P<0.05),而GATA-3、RORγt m RNA表达高于空白对照组(P<0.05)。五虎汤高、中剂量组脾组织GATA-3、RORγt m RNA表达均明显低于模型组(P<0.01或P<0.05),而T-bet、Foxp3 m RNA表达均明显高于模型组(P<0.01或P<0.05)。结论:五虎汤能调控病毒诱发幼年哮喘大鼠脾组织转录因子T-bet、GATA-3、RORγt、Foxp3 m RNA的表达,调控Thl、Th2、Thl7、Treg细胞,重建免疫平衡,抑制哮喘气道炎症形成。
