Electro-gene-transfer: A new approach for muscle gene delivery.
Electro-gene-transfer: A new approach for muscle gene delivery.
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DOI：
10.1023/a:1022927822244
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发表时间：
2002-11-01
期刊：
影响因子：
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通讯作者：
Toniatti, Carlo
中科院分区：
文献类型：
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作者：
Fattori, Elena;La Monica, Nicola;Toniatti, Carlo
通过直接注射裸露质粒 DNA 将基因转移到骨骼肌细胞中，导致基因持续表达。因此，肌肉注射质粒 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，该技术在人类基因应用中的潜在效用受到转导效率差以及基因表达水平低且高度可变的限制。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，通过在局部 DNA 注射后对肌肉纤维施加电场，可以显着改善 DNA 转移。电基因转移将基因表达提高了几个数量级，并大大降低了个体间的变异性。电注射编码分泌蛋白的基因可在基因治疗的动物模型中实现持续表达和疾病纠正。此外，当通过这种技术递送抗原编码质粒时，DNA疫苗的免疫原性显着增加。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。这篇综述简要概述了电基因转移理论，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通过电基因转移获得的结果，以及在考虑将其用于人类治疗之前必须解决的技术问题。
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.