Year: 2025
Type: article
Abstract: 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, PAH Enu2 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.
Authors: Efrain Guzman, Cheen Khoo, Deirdre O’Connor, Gayathri Devarajan, Sharifah Iqball, Bernard Souberbielle, Kyriacos Mitrophanous, Yatish Lad
Institution: Oxford BioMedica (United Kingdom)
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
OpenAlex ID: W4409825483