用于基因调节的纳米基核酸
Radhika Sharma1, Steven Narum2, Shuhong Liu1
1Department of Chemistry, Emory University, Atlanta, Georgia 30332, United States.
ACS chemical biology
|November 1, 2023
概括
我们开发了纳米片型核酸 (NNA) 以加强治疗性核酸的输送. 在体外和体内,NNAs表现出更好的稳定性,细胞吸收和强大的基因沉默.
科学领域:
- 生物技术是生物技术.
- 药物运输 药物运输 药物运输
- 分子生物学分子生物学
背景情况:
- 治疗性核酸提供基因表达控制,但面临的挑战是血清稳定性和内分体捕获.
- 脂质支架,如纳米光盘 (NDs),可以提高核酸输送效率.
- NDs是自组装的纳米结构,模仿高密度脂蛋白 (HDL).
研究的目的:
- 开发和表征纳米迪斯科伊德核酸 (NNA) 以改善治疗性核酸输送.
- 为了评估NNA稳定性,细胞吸收和治疗疗效.
- 评估NNA产生的反感性寡核酸的体内生物分布和治疗潜力.
主要方法:
- 纳米光盘 (NDs) 与寡核酸的共价修改,以创建NNAs.
- 使用FRET.评估核酶耐药性,通过清除受体B1进行细胞吸收,以及使用FRET.进行细胞内稳定性.
- 测试携带反感性寡核化物 (ASO) 的NNA,在细胞系中准HIF-1-α mRNA和3D癌症球状模型.
- 在动物模型中进行体内生物分布和基因沉默研究.
主要成果:
- 与可溶性核酸相比,NNAs表现出增强的核酶抵抗性和优越的细胞吸收.
- 内部化的NNA显示稳定性增加,FRET分析证实了这一点.
- ASO修饰的NNA在体外和体内都显示出HIF-1-αmRNA的强烈下调,在较低剂量时有效性得到改善.
- 在体内研究表明,在肝脏和脏的偏好局部化.
结论:
- 国家核酸代表了一个有前途的平台,可以更好地提供治疗性核酸.
- 该NNA技术克服了传统核酸疗法的关键局限性,包括稳定性和细胞进入.
- 在基因沉默应用中,NNA具有显著的治疗潜力,特别是在肝脏和脏向治疗中.
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