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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| _version_ | 1850156009106964480 |
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| author | Efrain Guzman Cheen Khoo Deirdre O’Connor Gayathri Devarajan Sharifah Iqball Bernard Souberbielle Kyriacos Mitrophanous Yatish Lad |
| author_facet | Efrain Guzman Cheen Khoo Deirdre O’Connor Gayathri Devarajan Sharifah Iqball Bernard Souberbielle Kyriacos Mitrophanous Yatish Lad |
| author_sort | Efrain Guzman |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-06f02adc8d9b40fbbf494edc0aacc65b |
| institution | OA Journals |
| issn | 1535-3699 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Experimental Biology and Medicine |
| spelling | doaj-art-06f02adc8d9b40fbbf494edc0aacc65b2025-08-20T02:24:43ZengFrontiers Media S.A.Experimental Biology and Medicine1535-36992025-04-0125010.3389/ebm.2025.1042210422Gender difference in pre-clinical liver-directed gene therapy with lentiviral vectorsEfrain GuzmanCheen KhooDeirdre O’ConnorGayathri DevarajanSharifah IqballBernard SouberbielleKyriacos MitrophanousYatish LadViral 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.https://www.ebm-journal.org/articles/10.3389/ebm.2025.10422/fulllentiviral vectorsadeno-associated virusAAVliverPAHgender |
| spellingShingle | Efrain Guzman Cheen Khoo Deirdre O’Connor Gayathri Devarajan Sharifah Iqball Bernard Souberbielle Kyriacos Mitrophanous Yatish Lad Gender difference in pre-clinical liver-directed gene therapy with lentiviral vectors Experimental Biology and Medicine lentiviral vectors adeno-associated virus AAV liver PAH gender |
| title | Gender difference in pre-clinical liver-directed gene therapy with lentiviral vectors |
| title_full | Gender difference in pre-clinical liver-directed gene therapy with lentiviral vectors |
| title_fullStr | Gender difference in pre-clinical liver-directed gene therapy with lentiviral vectors |
| title_full_unstemmed | Gender difference in pre-clinical liver-directed gene therapy with lentiviral vectors |
| title_short | Gender difference in pre-clinical liver-directed gene therapy with lentiviral vectors |
| title_sort | gender difference in pre clinical liver directed gene therapy with lentiviral vectors |
| topic | lentiviral vectors adeno-associated virus AAV liver PAH gender |
| url | https://www.ebm-journal.org/articles/10.3389/ebm.2025.10422/full |
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