通过向纳米颗粒系统管理siRNA的人类RNAi的证据
Mark E Davis1, Jonathan E Zuckerman, Chung Hang J Choi
1Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA. mdavis@cheme.caltech.edu
Nature
|March 23, 2010
概括
癌症患者的系统性小干扰RNA (siRNA) 治疗表明了RNA干扰 (RNAi) 作用机制. 这项研究表明,siRNA有效地降低了人类的目标mRNA和蛋白质水平,这标志着RNAi疗法的重大进步.
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 是一个遗传学.
背景情况:
- RNA干扰 (RNAi) 疗法提供了新的治疗策略.
- 小干扰RNAs (siRNAs) 可以在没有干扰素反应的情况下在哺乳动物细胞中引起RNAi.
- 目前正在研究用于癌症治疗的siRNA的系统输送.
研究的目的:
- 为了提供RNAi作用机制在人类系统性siRNA管理后的证据.
- 评估纳米粒子输送siRNA在癌症患者中的疗效.
- 为了评估针对siRNA治疗的目标基因和蛋白质减少.
主要方法:
- 在黑色素瘤患者的系统性siRNA管理的I期临床试验.
- 利用了针对siRNA.RNA的向纳米粒子传递系统.
- 分析了纳米粒子定位的瘤活检,mRNA和蛋白质水平 (RRM2),以及siRNA介导的裂变产品.
主要成果:
- 在瘤活检中发现了细胞内纳米颗粒,与给药剂量相关.
- 治疗后观察到RRM2信使RNA和蛋白质水平的显著降低.
- 在高剂量患者中检测到的mRNA片段证实了在预测位置的siRNA介导裂变.
结论:
- 系统性siRNA的管理可以诱导一种特定的RNAi作用机制在人类.
- 在癌症患者中通过RNAi证明了成功的基因抑制 (mRNA和蛋白质减少).
- 这项研究是系统输送纳米颗粒的首例,为基于siRNA的癌症治疗提供了证据.
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