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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月10日

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

摘要

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.