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热稳定性和ssDNA加载的腺相关病毒体的动力学:一个粗粒度的分子动力学模拟

Tibo Duran¹, Shivangi Naik², Willow DiLuzio²

¹Department of Pharmaceutical Sciences, School of Pharmacy, Massachusetts College of Pharmacy and Health Sciences University, Boston, MA 02115, USA.

International journal of pharmaceutics

|November 12, 2025

概括

高温破坏了腺相关病毒 (AAV) 囊的稳定性,导致基因组释放. 分子动力学模拟显示了温度依赖的结构分解和DNA扩张,影响了体的完整性.

科学领域:

结构生物学是结构生物学.
生物物理学的生物物理.
计算病毒学计算病毒学.

背景情况:

基因相关病毒 (AAV) 是基因治疗的多功能载体.
了解AAV囊体稳定性对于有效的治疗提供至关重要.
之前的研究已经探讨了AAV的稳定性,但温度诱导的分解的详细机制仍然不完全理解.

研究的目的:

为了研究AAV体的结构分解作为温度的函数.
阐明在水性环境中从AAV释放基因组的机制.
分析单链DNA (ssDNA) 在不同温度下对体稳定性的影响.

主要方法:

使用粗粒度分子动力学 (CG-MD) 模拟.
在装载ssDNA的AAV8体上进行了模拟.
研究的温度包括300 K,338 K和363 K超过10微秒.

主要成果:

高温 (338 K和363 K) 削弱了体结构,导致蛋白质子单元的不稳定性和结构变化增加.
观察到ssDNA的热膨胀,有助于5倍层结构的崩.
ssDNA不对称性可能导致囊形状的扭曲,进一步促进结构失灵和基因组泄漏.

结论:

该研究提供了一个详细的计算框架,以了解AAV的结构稳定性和温度依赖的体破裂.
这些发现强调了温度和ssDNA特性在AAV基因组释放机制中的关键作用.
这项研究推进了与AAV基因疗法的设计和应用相关的知识.

关键词:

腺相关病毒的病毒.卡普西德破裂的破裂情况发生DNA泄漏.分子动力学模拟的模拟.单链DNA是一种单链DNA.

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