通过模仿逆转录病毒在哺乳动物细胞中产生具有功能活动的DNA Aptamers
Neng Ling1, Huiming Liu1, Junxiao Guo1
1Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China.
Analytical chemistry
|June 16, 2023
概括
研究人员开发了一种用于细胞内使用的新型DNA体表达系统. 这个系统成功地在哺乳动物细胞中产生了功能性DNA体,抑制了癌细胞的增殖,并提供了新的治疗途径.
科学领域:
- 生物技术是生物技术.
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- DNA 体是具有高目标亲和度的 DNA 序列,通常通过体外合成产生.
- 目前细胞内DNA阿巴特马生成的局限性阻碍了它们用于持续蛋白质活性调节的临床应用.
- 现有的方法在实现DNA体的长期细胞内作用方面面临挑战.
研究的目的:
- 开发一种新的DNA体表达系统,用于在哺乳动物细胞内产生功能性DNA体.
- 为了证明针对特定蛋白质的DNA吸收体的细胞内生成和活性.
- 探索该系统在治疗应用中的潜力,特别是在癌症治疗中.
主要方法:
- 模仿逆转录病毒机制,为细胞内生产设计了一种DNA体表达系统.
- 在细胞中成功生成了向细胞内Ras (Ra1) 和膜结合的CD71 (XQ2) 的DNA吸收体.
- 一种lentivirus载体被用来提供DNA的aptamer表达系统,以实现稳定,长期的表达.
主要成果:
- 细胞内表达的Ra1胺酶特异地与Ras蛋白结合,并抑制下游信号传递 (ERK1/2和AKT酸化).
- 通过lentiviral递送Ra1的稳定表达导致抑制肺癌细胞增殖.
- 该系统在细胞环境中成功生成了功能性DNA体.
结论:
- 在哺乳动物细胞中建立了一种具有功能活性的细胞内DNA胺生成的新策略.
- 这个系统克服了体外合成的局限性,使得持续的细胞内效应.
- 这些发现为细胞内DNA体在疾病治疗,包括癌症治疗中的临床应用开辟了新的可能性.
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