猪报告模型用于基因传递载体的临床前评估和表征
Jarryd M Campbell1, Derek M Korpela1, Hesong Han2,3
1Recombinetics, Eagan, MN, USA.
bioRxiv : the preprint server for biology
|July 15, 2025
概括
一种新的猪报告模型 (SRM-1) 能够精确跟踪大型动物的基因治疗载体传递. 该工具通过评估病毒和非病毒载体的有效性和安全性,有助于推进遗传药物.
科学领域:
- 生物技术是生物技术.
- 基因治疗 基因治疗
- 动物模型 动物模型
背景情况:
- 将基因疗法载体传递到体细胞是遗传医学发展的一个重大挑战.
- 由于解剖学和生理学差异,动物模型在预测人类翻译方面存在局限性,需要进行大型动物研究.
研究的目的:
- 开发和验证一种猪报告模型 (SRM-1),用于在大型动物系统中评估体内基因治疗载体的传递.
- 评估SRM-1模型在追踪细胞特异向量传递和表达方面的实用性.
主要方法:
- 在Rosa26位点使用Cre和CRISPR激活的tdTomato记者开发猪记者模型 (SRM-1).
- 系统注射腺相关病毒9型血清 (AAV9) 和携带mRNA的脂质纳米粒子 (LNP).
- 脑内静脉内 (ICV) 给药LNP-Cre mRNA. 在脑内静脉内 (ICV) 给予.
主要成果:
- 在系统性AAV9和LNP给药后,在多种组织中成功激活体内记者.
- 在ICV给予LNP-CremRNA后,在皮层脑细胞中局部的记者激活.
- 证明了SRM-1模型的生物分布和细胞特异性表达追踪能力.
结论:
- 在大型动物模型中,SRM-1模型是一个有价值的临床前工具,用于评估基因治疗载体的传递,生物分布和安全性.
- 该模型支持基因疗法的进步,从临床前研究到临床应用.
- 该SRM-1模型有助于测试各种施用方法,包括手术和非手术方法.
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