以AAV5作为冷解药物产品的配方开发和可行性
Stephanie K Vargas1, Farrokh Sharifi2, Reinard Nambayan2
1Drug Product and Device Technologies, BioMarin Pharmaceutical Inc., 105 Digital Drive, Novato, CA 94949 USA; Department of Pharmaceutical Chemistry, School of Pharmacy, The University of Kansas, 2095 Constant Avenue, Lawrence, KS 66047 USA.
Journal of pharmaceutical sciences
|January 19, 2025
概括
软化为冷腺相关病毒 (AAV) 基因疗法提供了一个稳定的替代方案,使得更容易分布. 特定的辅助剂,如二和三糖,在冷干燥和储存过程中有效地保持了AAV5囊体的完整性.
科学领域:
- 生物技术是生物技术.
- 基因治疗 基因治疗
- 制药配方 制药配方 制药配方
背景情况:
- 目前的腺关联病毒 (AAV) 基因疗法依赖于冷配方,这给全球分布和储存带来了重大挑战.
- 化 (冷干燥) 是一种有希望的替代方案,可以实现长期的冷藏储存,并提高基于AAV的治疗药物的保质期,从而潜在地降低整体成本.
研究的目的:
- 为了评估冷化的可行性,以稳定腺相关病毒血清型5 (AAV5) 基因疗法产品.
- 评估各种辅助剂在化过程中和之后以及随后的储存期间保持AAV5囊完整性的有效性.
主要方法:
- 采用了一系列生物物理技术来分析AAV5体完整性,包括对外部化DNA的量化,体颗粒大小分析和体单体百分比分析.
- 使用传输电子显微镜 (TEM) 可视化和评估经过冷化处理的AAV5体的大小和结构完整性,证实了其他方法的发现.
主要成果:
- 一种含有素和三糖的配方在溶解后立即证明了AAV5体结构的有效稳定,体空白最小,外部DNA水平低.
- 一种含有复合人体白蛋白和三糖的配方显示,随着时间的推移,体结构稳定性得到改善,由更好的外部DNA配置文件和单体完整性证明.
- 相反,观察到曼尼的结晶对AAV5体结构有不利影响.
结论:
- 冷化是稳定腺相关病毒 (AAV5) 药物产品的可行和有效方法,为传统冷配方提供了切实可行的替代方案.
- 选择合适的辅助剂,如基/三糖或白蛋白/三糖组合,对于成功的AAV5冷化和长期储存稳定性至关重要.
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