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缺氧和HIF-1抑制增强慢病毒转导效率：一种优化基因递送的新策略。

Hypoxia and HIF-1 inhibition enhance lentiviral transduction efficiency: a novel strategy for gene delivery optimization.

作者信息

Huo Qianyu, Wang Wentian, Dai Jiawen, Yuan Xu, Yu Dandan, Xu Bingqi, Chi Ying, Li Huiyuan, Pei Xiao Lei, Zhu Guoqing, Zhang Lei

机构信息

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Tianjin & CAMS Key Laboratory of Gene Therapy for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China.

School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300020, China.

出版信息

BMC Biotechnol. 2025 May 10;25(1):34. doi: 10.1186/s12896-025-00969-3.

DOI:10.1186/s12896-025-00969-3
PMID:40346583
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12065270/
Abstract

Lentiviral vectors are widely used for stable gene delivery, but their transduction efficiency can be limited by suboptimal experimental conditions. Here, we investigated the role of oxygen concentration and hypoxia-inducible factor 1 (HIF-1) signaling in lentiviral packaging and transduction. We found that packaging lentivirus under hypoxic conditions (10% O₂) significantly increased viral titers and transduction efficiency by approximately 10%. However, hypoxic conditions during viral entry impaired infection efficiency, likely due to HIF-1α-mediated cellular protective mechanisms. Pretreatment of cells with the HIF-1 inhibitor PX-478 reversed this effect, enhancing viral entry and genome integration in a dose-dependent manner. Combining hypoxic virus packaging with PX-478 pretreatment synergistically improved transduction efficiency by 20%. These findings suggest that HIF-1 inhibition and controlled hypoxia significantly enhance lentiviral transduction efficiency, establishing a versatile strategy with broad applicability across viral vector-dependent biomedical applications.

摘要

慢病毒载体被广泛用于稳定的基因传递，但其转导效率可能受到不理想的实验条件限制。在此，我们研究了氧浓度和缺氧诱导因子1（HIF-1）信号在慢病毒包装和转导中的作用。我们发现，在低氧条件（10% O₂）下包装慢病毒显著提高了病毒滴度和转导效率，约提高了10%。然而，病毒进入过程中的低氧条件损害了感染效率，这可能是由于HIF-1α介导的细胞保护机制所致。用HIF-1抑制剂PX-478预处理细胞可逆转这种效应，以剂量依赖的方式增强病毒进入和基因组整合。将低氧病毒包装与PX-478预处理相结合可协同提高20%的转导效率。这些发现表明，抑制HIF-1和控制低氧可显著提高慢病毒转导效率，从而建立了一种具有广泛适用性的通用策略，可应用于各种依赖病毒载体的生物医学应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f52/12065270/239a6b97f9d9/12896_2025_969_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f52/12065270/1ecd52558b99/12896_2025_969_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f52/12065270/81958302dff9/12896_2025_969_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f52/12065270/43fffc9694d2/12896_2025_969_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f52/12065270/239a6b97f9d9/12896_2025_969_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f52/12065270/1ecd52558b99/12896_2025_969_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f52/12065270/81958302dff9/12896_2025_969_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f52/12065270/43fffc9694d2/12896_2025_969_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f52/12065270/239a6b97f9d9/12896_2025_969_Fig4_HTML.jpg

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