{"title":"以反义寡核苷酸为基础的治疗方法面临的挑战,特别是杜氏肌营养不良的51外显子跳跃","authors":"Y. Aoki, T. Nagata, Y. Shimizu, S. Takeda","doi":"10.1109/ICMSAO.2011.5775520","DOIUrl":null,"url":null,"abstract":"Duchenne muscular dystrophy (DMD) is a lethal muscle disorder characterized by mutations in the DMD gene. These mutations primarily disrupt the reading frame, leading to an absence of functional dystrophin protein. Exon-skipping through the use of antisense oligonucleotides has served as a promising therapeutic approach for DMD, and clinical trials in DMD patients are currently underway. Recently, stable and less-toxic antisense oligonucleotides have been developed with a higher efficacy in mouse and dog models of DMD. Despite these advancements, this therapeutic approach is limited by relatively poor systemic delivery of antisense oligonucleotides to muscle, as well as toxicity effects. This review highlights the challenges for antisense oligonucleotide-based therapeutics for DMD, in particular with methods using exon 51-skipping.","PeriodicalId":6383,"journal":{"name":"2011 Fourth International Conference on Modeling, Simulation and Applied Optimization","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2011-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Challenges for antisense oligonucleotide-based therapeutics, in particular for exon 51-skipping in Duchenne muscular dystrophy\",\"authors\":\"Y. Aoki, T. Nagata, Y. Shimizu, S. Takeda\",\"doi\":\"10.1109/ICMSAO.2011.5775520\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Duchenne muscular dystrophy (DMD) is a lethal muscle disorder characterized by mutations in the DMD gene. These mutations primarily disrupt the reading frame, leading to an absence of functional dystrophin protein. Exon-skipping through the use of antisense oligonucleotides has served as a promising therapeutic approach for DMD, and clinical trials in DMD patients are currently underway. Recently, stable and less-toxic antisense oligonucleotides have been developed with a higher efficacy in mouse and dog models of DMD. Despite these advancements, this therapeutic approach is limited by relatively poor systemic delivery of antisense oligonucleotides to muscle, as well as toxicity effects. This review highlights the challenges for antisense oligonucleotide-based therapeutics for DMD, in particular with methods using exon 51-skipping.\",\"PeriodicalId\":6383,\"journal\":{\"name\":\"2011 Fourth International Conference on Modeling, Simulation and Applied Optimization\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2011-04-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"2011 Fourth International Conference on Modeling, Simulation and Applied Optimization\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1109/ICMSAO.2011.5775520\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"2011 Fourth International Conference on Modeling, Simulation and Applied Optimization","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1109/ICMSAO.2011.5775520","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Challenges for antisense oligonucleotide-based therapeutics, in particular for exon 51-skipping in Duchenne muscular dystrophy
Duchenne muscular dystrophy (DMD) is a lethal muscle disorder characterized by mutations in the DMD gene. These mutations primarily disrupt the reading frame, leading to an absence of functional dystrophin protein. Exon-skipping through the use of antisense oligonucleotides has served as a promising therapeutic approach for DMD, and clinical trials in DMD patients are currently underway. Recently, stable and less-toxic antisense oligonucleotides have been developed with a higher efficacy in mouse and dog models of DMD. Despite these advancements, this therapeutic approach is limited by relatively poor systemic delivery of antisense oligonucleotides to muscle, as well as toxicity effects. This review highlights the challenges for antisense oligonucleotide-based therapeutics for DMD, in particular with methods using exon 51-skipping.