Laura Torella, Julia Klermund, Martin Bilbao-Arribas, Ibon Tamayo, Geoffroy Andrieux, Kay O Chmielewski, Africa Vales, Cristina Olagüe, Daniel Moreno-Luqui, Ivan Raimondi, Amaya Abad, Julen Torrens-Baile, Eduardo Salido, Maite Huarte, Mikel Hernaez, Melanie Boerries, Toni Cathomen, Nerea Zabaleta, Gloria Gonzalez-Aseguinolaza
The therapeutic use of adeno-associated viral vector (AAV)-mediated gene disruption using CRISPR-Cas9 is limited by potential off-target modifications and the risk of uncontrolled integration of vector genomes into CRISPR-mediated double-strand breaks. To address these concerns, we explored the use of AAV-delivered paired Staphylococcus aureus nickases (D10ASaCas9) to target the Hao1 gene for the treatment of primary hyperoxaluria type 1 (PH1). Our study demonstrated effective Hao1 gene disruption, a significant decrease in glycolate oxidase expression, and a therapeutic effect in PH1 mice...
January 5, 2024: EMBO Molecular Medicine