Gender difference in pre-clinical liver-directed gene therapy with lentiviral vectors
Viral vector-based therapies are effective therapeutics for the correction of several disorders, both in mouse models and in humans. Several pre-clinical studies have demonstrated differences in transduction efficiencies and therapeutic effect between male and female mice dosed with AAV-based gene t...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-04-01
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| Series: | Experimental Biology and Medicine |
| Subjects: | |
| Online Access: | https://www.ebm-journal.org/articles/10.3389/ebm.2025.10422/full |
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| Summary: | Viral vector-based therapies are effective therapeutics for the correction of several disorders, both in mouse models and in humans. Several pre-clinical studies have demonstrated differences in transduction efficiencies and therapeutic effect between male and female mice dosed with AAV-based gene therapy product candidates. Here, we report gender-specific transduction and transgene expression differences in mice dosed systemically with lentiviral vectors (LVV). Male mice systemically dosed with LVV carrying the reporter gene luciferase showed at least a 12-fold higher expression of luciferase and a higher vector copy number (VCN) in their livers compared with female mice. Lastly, PAHEnu2 male mice dosed with a LVV carrying the human phenylalanine hydroxylase (PAH) transgene were observed to have a higher VCN than their female littermates. These findings suggest that sex-based differences initially observed in AAV-mediated therapies also apply to LVV, but the exact mechanism remains to be determined. |
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| ISSN: | 1535-3699 |