Takahashi Yuki, Nishikawa Makiya, Takakura Yoshinobu
Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
Front Biosci (Schol Ed). 2012 Jan 1;4(1):133-41. doi: 10.2741/256.
Nonviral gene therapy is expected to become a regular treatment for a variety of difficult-to-treat diseases, such as cancer and virus infection. Plasmid DNA, which is used in most nonviral gene delivery systems, usually contains, unmethylated cytosine-guanine dinucleotides, so called CpG motifs. CpG motifs are recognized by immune cells as a danger signal, leading to an inflammatory response. Such inflammatory responses could affect the safety and effectiveness of nonviral gene therapy. Therefore, reducing the number of CpG motifs in plasmid DNA has been used to increase the potency of plasmid DNA-based gene therapy. Previous studies have demonstrated that CpG reduction can extend the time period of transgene expression from plasmid DNA after in vivo gene transfer. In this review, the biological functions of the CpG motif are briefly summarized. Then, safety issues of nonviral gene therapy are discussed from the viewpoint of the inflammatory response to the CpG motif in plasmid DNA, and the effects of the CpG motif in plasmid DNA on the transgene expression profile of nonviral gene transfer are reviewed.
非病毒基因疗法有望成为治疗多种难治性疾病（如癌症和病毒感染）的常规疗法。大多数非病毒基因递送系统中使用的质粒DNA通常含有未甲基化的胞嘧啶-鸟嘌呤二核苷酸，即所谓的CpG基序。CpG基序被免疫细胞识别为危险信号，从而引发炎症反应。这种炎症反应可能会影响非病毒基因疗法的安全性和有效性。因此，减少质粒DNA中CpG基序的数量已被用于提高基于质粒DNA的基因疗法的效力。先前的研究表明，降低CpG含量可以延长体内基因转移后质粒DNA转基因表达的时间。在这篇综述中，简要总结了CpG基序的生物学功能。然后，从对质粒DNA中CpG基序的炎症反应角度讨论了非病毒基因疗法的安全性问题，并综述了质粒DNA中CpG基序对非病毒基因转移转基因表达谱的影响。
