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通过纳米颗粒传递的mRNA编码一种在迟缓生物中发现的破坏抑制蛋白质,对健康组织进行辐射保护

Ameya R Kirtane^1,2, Jianling Bi^3,4,5, Netra U Rajesh^2,6,7

¹Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Nature biomedical engineering

|February 26, 2025

概括

科学家们开发了一种新方法,可以在癌症治疗期间保护健康组织免受辐射损伤. 这种方法使用一种通过信使RNA传递的灵感来自于迟的蛋白质来减少正常细胞中的DNA断裂,保持治疗的有效性.

科学领域:

生物医学工程生物医学工程
分子生物学分子生物学
辐射瘤学辐射瘤学

背景情况:

癌症的放射治疗可能会导致严重的副作用,原因是瘤周围健康组织的DNA损伤.
尾动物拥有一种独特的蛋白质,可以保护它们的DNA免受极端辐射暴露.

研究的目的:

为了研究一种来自迟的抑制损伤蛋白的潜力,以保护正常组织免受辐射诱导的DNA损伤.
在临床前模型中评估这种蛋白质基于信使RNA (mRNA) 输送的疗效.

主要方法:

使用可电离的脂质纳米颗粒和可生物降解的阴离子聚合物,以有效地将mRNA输入口腔和直肠上皮细胞.
在小鼠的口腔和直肠组织中局部和暂时编码破坏抑制蛋白的mRNA.
在正管口腔癌模型中评估了辐射保护作用和辐射疗法疗效的保存.

主要成果:

证明损害抑制蛋白的局部和短暂表达显著减少了上皮组织中辐射诱导的DNA链断裂.
展示了基于mRNA的正常组织的辐射保护不会影响小鼠辐射治疗的抗癌疗效.
在目标组织中确认了保护蛋白的成功输送和表达.

结论:

通过mRNA传递的虫灵感的破坏抑制蛋白质提供了一种有希望的策略,用于减轻正常组织中的辐射毒性.
这种方法有可能在放射治疗期间保护健康组织,治疗各种癌症,如头癌和前列腺癌.
该策略可能广泛适用于保护健康组织免受其他破坏DNA的毒素.

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