{"title":"合成聚合物输送 RNA 的趋势。","authors":"Josh J. Friesen, Anna K. Blakney","doi":"10.1002/jgm.3672","DOIUrl":null,"url":null,"abstract":"<p>Ribonucleic acid (RNA) has emerged as one of the most promising therapeutic payloads in the field of gene therapy. There are many unique types of RNA that allow for a range of applications including vaccination, protein replacement therapy, autoimmune disease treatment, gene knockdown and gene editing. However, RNA triggers the host immune system, is vulnerable to degradation and has a low proclivity to enter cells spontaneously. Therefore, a delivery vehicle is required to facilitate the protection and uptake of RNA therapeutics into the desired host cells. Lipid nanoparticles have emerged as one of the only clinically approved vehicles for genetic payloads, including in the COVID-19 messenger RNA vaccines. While lipid nanoparticles have distinct advantages, they also have drawbacks, including strong immune stimulation, complex manufacturing and formulation heterogeneity. In contrast, synthetic polymers are a widely studied group of gene delivery vehicles and boast distinct advantages, including biocompatibility, tunability, inexpensiveness, simple formulation and ease of modification. Some classes of polymers enhance efficient transfection efficiency, and lead to lower stimulation of the host immune system, making them more viable candidates for non-vaccine-related applications of RNA medicines. This review aims to identify the most promising classes of synthetic polymers, summarize recent research aimed at moving them into the clinic and postulate the future steps required for unlocking their full potential.</p>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jgm.3672","citationCount":"0","resultStr":"{\"title\":\"Trends in the synthetic polymer delivery of RNA\",\"authors\":\"Josh J. Friesen, Anna K. Blakney\",\"doi\":\"10.1002/jgm.3672\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Ribonucleic acid (RNA) has emerged as one of the most promising therapeutic payloads in the field of gene therapy. There are many unique types of RNA that allow for a range of applications including vaccination, protein replacement therapy, autoimmune disease treatment, gene knockdown and gene editing. However, RNA triggers the host immune system, is vulnerable to degradation and has a low proclivity to enter cells spontaneously. Therefore, a delivery vehicle is required to facilitate the protection and uptake of RNA therapeutics into the desired host cells. Lipid nanoparticles have emerged as one of the only clinically approved vehicles for genetic payloads, including in the COVID-19 messenger RNA vaccines. While lipid nanoparticles have distinct advantages, they also have drawbacks, including strong immune stimulation, complex manufacturing and formulation heterogeneity. In contrast, synthetic polymers are a widely studied group of gene delivery vehicles and boast distinct advantages, including biocompatibility, tunability, inexpensiveness, simple formulation and ease of modification. Some classes of polymers enhance efficient transfection efficiency, and lead to lower stimulation of the host immune system, making them more viable candidates for non-vaccine-related applications of RNA medicines. This review aims to identify the most promising classes of synthetic polymers, summarize recent research aimed at moving them into the clinic and postulate the future steps required for unlocking their full potential.</p>\",\"PeriodicalId\":56122,\"journal\":{\"name\":\"Journal of Gene Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-02-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jgm.3672\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Gene Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jgm.3672\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Gene Medicine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jgm.3672","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
Ribonucleic acid (RNA) has emerged as one of the most promising therapeutic payloads in the field of gene therapy. There are many unique types of RNA that allow for a range of applications including vaccination, protein replacement therapy, autoimmune disease treatment, gene knockdown and gene editing. However, RNA triggers the host immune system, is vulnerable to degradation and has a low proclivity to enter cells spontaneously. Therefore, a delivery vehicle is required to facilitate the protection and uptake of RNA therapeutics into the desired host cells. Lipid nanoparticles have emerged as one of the only clinically approved vehicles for genetic payloads, including in the COVID-19 messenger RNA vaccines. While lipid nanoparticles have distinct advantages, they also have drawbacks, including strong immune stimulation, complex manufacturing and formulation heterogeneity. In contrast, synthetic polymers are a widely studied group of gene delivery vehicles and boast distinct advantages, including biocompatibility, tunability, inexpensiveness, simple formulation and ease of modification. Some classes of polymers enhance efficient transfection efficiency, and lead to lower stimulation of the host immune system, making them more viable candidates for non-vaccine-related applications of RNA medicines. This review aims to identify the most promising classes of synthetic polymers, summarize recent research aimed at moving them into the clinic and postulate the future steps required for unlocking their full potential.
期刊介绍:
The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies.
Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials.
Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.