电基因转移:肌肉基因传递的新途径。

Elena Fattori, Nicola La Monica, Gennaro Ciliberto, Carlo Toniatti
{"title":"电基因转移:肌肉基因传递的新途径。","authors":"Elena Fattori,&nbsp;Nicola La Monica,&nbsp;Gennaro Ciliberto,&nbsp;Carlo Toniatti","doi":"10.1023/a:1022927822244","DOIUrl":null,"url":null,"abstract":"<p><p>Gene transfer into skeletal muscle cells by direct injection of naked plasmid DNA results in sustained gene expression. Intramuscular injection of plasmid DNA might thus be used to correct myopathies, to secrete locally or systematic therapeutic proteins and to elicit an immune response against specific antigens. However, the potential utility of this technique for gene application in humans is limited by the poor transduction efficiency and the low and highly variable level of gene expression. Different methods are thus being developed to increase the efficiency of gene transfer in muscles. It has been recently reported that a dramatic improvement of DNA transfer is achieved by applying an electric field to the muscle fibers subsequent to local DNA injection. Electro-gene-transfer increases gene expression by several orders of magnitude and strongly reduces interindividual variability. Electroinjection of genes encoding for secreted proteins resulted in sustained expression and disease correction in animal models of gene therapy. Moreover, the immunogenicity of DNA vaccines is dramatically increased when antigen-encoding plasmids are delivered by this technique. This technique may thus have broad and important applications in human gene therapy. This review provides a brief overview of the theory of electro-gene-transfer and describes parameters governing its efficiency in muscle. We also summarize the results obtained with electro-gene-transfer in animal models to date and the technical issues that must be solved before its use for human therapy can be considered.</p>","PeriodicalId":21884,"journal":{"name":"Somatic Cell and Molecular Genetics","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2002-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1023/a:1022927822244","citationCount":"45","resultStr":"{\"title\":\"Electro-gene-transfer: a new approach for muscle gene delivery.\",\"authors\":\"Elena Fattori,&nbsp;Nicola La Monica,&nbsp;Gennaro Ciliberto,&nbsp;Carlo Toniatti\",\"doi\":\"10.1023/a:1022927822244\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Gene transfer into skeletal muscle cells by direct injection of naked plasmid DNA results in sustained gene expression. Intramuscular injection of plasmid DNA might thus be used to correct myopathies, to secrete locally or systematic therapeutic proteins and to elicit an immune response against specific antigens. However, the potential utility of this technique for gene application in humans is limited by the poor transduction efficiency and the low and highly variable level of gene expression. Different methods are thus being developed to increase the efficiency of gene transfer in muscles. It has been recently reported that a dramatic improvement of DNA transfer is achieved by applying an electric field to the muscle fibers subsequent to local DNA injection. Electro-gene-transfer increases gene expression by several orders of magnitude and strongly reduces interindividual variability. Electroinjection of genes encoding for secreted proteins resulted in sustained expression and disease correction in animal models of gene therapy. Moreover, the immunogenicity of DNA vaccines is dramatically increased when antigen-encoding plasmids are delivered by this technique. This technique may thus have broad and important applications in human gene therapy. This review provides a brief overview of the theory of electro-gene-transfer and describes parameters governing its efficiency in muscle. We also summarize the results obtained with electro-gene-transfer in animal models to date and the technical issues that must be solved before its use for human therapy can be considered.</p>\",\"PeriodicalId\":21884,\"journal\":{\"name\":\"Somatic Cell and Molecular Genetics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2002-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1023/a:1022927822244\",\"citationCount\":\"45\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Somatic Cell and Molecular Genetics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1023/a:1022927822244\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Somatic Cell and Molecular Genetics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1023/a:1022927822244","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 45

摘要

通过直接注射裸质粒DNA将基因转移到骨骼肌细胞中,可获得持续的基因表达。因此,肌内注射质粒DNA可能用于纠正肌病,分泌局部或系统治疗蛋白,并引发针对特定抗原的免疫反应。然而,这种技术在人类基因应用中的潜在效用受到转导效率低和基因表达水平高低可变的限制。因此,人们正在开发不同的方法来提高肌肉中基因转移的效率。最近有报道称,在局部注射DNA后,在肌肉纤维上施加电场可以显著改善DNA转移。电基因转移增加了几个数量级的基因表达,并大大减少了个体间的差异。在基因治疗动物模型中,电注射编码分泌蛋白的基因导致持续表达和疾病纠正。此外,当抗原编码质粒通过这种技术传递时,DNA疫苗的免疫原性显著提高。因此,这项技术可能在人类基因治疗中具有广泛而重要的应用。本文综述了电基因传递理论的简要概述,并描述了控制其在肌肉中的效率的参数。我们还总结了迄今为止在动物模型中获得的电基因转移的结果,以及在将其用于人类治疗之前必须解决的技术问题。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Electro-gene-transfer: a new approach for muscle gene delivery.

Gene transfer into skeletal muscle cells by direct injection of naked plasmid DNA results in sustained gene expression. Intramuscular injection of plasmid DNA might thus be used to correct myopathies, to secrete locally or systematic therapeutic proteins and to elicit an immune response against specific antigens. However, the potential utility of this technique for gene application in humans is limited by the poor transduction efficiency and the low and highly variable level of gene expression. Different methods are thus being developed to increase the efficiency of gene transfer in muscles. It has been recently reported that a dramatic improvement of DNA transfer is achieved by applying an electric field to the muscle fibers subsequent to local DNA injection. Electro-gene-transfer increases gene expression by several orders of magnitude and strongly reduces interindividual variability. Electroinjection of genes encoding for secreted proteins resulted in sustained expression and disease correction in animal models of gene therapy. Moreover, the immunogenicity of DNA vaccines is dramatically increased when antigen-encoding plasmids are delivered by this technique. This technique may thus have broad and important applications in human gene therapy. This review provides a brief overview of the theory of electro-gene-transfer and describes parameters governing its efficiency in muscle. We also summarize the results obtained with electro-gene-transfer in animal models to date and the technical issues that must be solved before its use for human therapy can be considered.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信