脂性和酸盐脊柱修改组合对修改过的寡核酸细胞吸收的影响
Timofey D Zharkov1, Oleg V Markov1, Sergey A Zhukov1
1Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of RAS, Lavrentiev Ave. 8, 630090 Novosibirsk, Russia.
Molecules (Basel, Switzerland)
|January 23, 2024
概括
橄核酸的修改,包括脂性和酸盐骨干的变化,显著影响细胞透和特性. 结合这些修改,为设计具有特定细胞吸收效率的核酸结构提供了一个强大的策略.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 氧核酸合成的合成方法
背景情况:
- 自动合成使得多种类型的寡核酸基因改造成为可能.
- 关于这些修改对核酸性质的综合影响的研究有限.
- 了解修改影响对于开发有效的核酸疗法至关重要.
研究的目的:
- 为了合成具有3'-end脂性和酸盐脊柱改性组合的寡核酸.
- 评估这些组合修改如何影响细胞透效率.
- 探索改造组合的潜力,以合理设计核酸结构.
主要方法:
- 合成含有胆固醇或十二残留在3'-end的寡核酸.
- 在不同的位置加入各种酸盐骨干修改.
- 对改性寡核酸的细胞吸收效率的评估.
主要成果:
- 脂性和酸盐修饰的组合显著改变了寡核酸的特性.
- 即使是少数酸盐修饰也可以显著影响细胞吸收.
- 不同的修饰类型之间的相互作用会影响整体的寡核酸行为.
结论:
- 组合的寡核酸修饰为定制性质提供了一种多功能策略.
- 使用修改组合的理性设计可以增强细胞输送核酸.
- 这种方法对开发先进的基于寡核酸的治疗方法具有前景.
相关概念视频
Receptor-mediated Endocytosis
104.5K
Overview
104.5K
Drug Biotransformation: Overview
2.4K
Pharmaceutical substances known as xenobiotics are predominantly lipophilic and nonionized. This enables them to permeate lipid bilayers, such as cell membranes, and interact with intracellular target receptors. Lipophilic drugs have an advantage in crossing biological barriers and reaching their intended sites of action. However, lipophilic drugs often have a restricted capacity for renal expulsion or elimination from the body. When these drugs enter the kidneys and undergo glomerular...
2.4K
Cellular Membranes and Drug Transport
560
Drugs must traverse multiple biological barriers, such as multi-layered skin, single-layered intestinal epithelium, and the plasma membrane, to reach their target sites within the body. The plasma membrane, a highly structured composite of phospholipids, carbohydrates, and proteins, is the cell's protective boundary, facilitating selective substance exchange.
Phospholipids arrange themselves into a bilayer, with hydrophilic heads oriented outward and hydrophobic tails facing inward.
Phospholipids arrange themselves into a bilayer, with hydrophilic heads oriented outward and hydrophobic tails facing inward.
560


