Cantore, A., Milani, M., Liu, T., Della Valle, P., D'Angelo, A., VandenDriessche, T., Chuah, M., Jiang, H., Nichols, T., & Naldini, L. (2015). Intravenous administration of lentiviral vectors expressing hyperfunctional factor IX converts severe into mild hemophilia B in a canine model. Human Gene Therapy, 26(10), A30-A30.

@article{1a343ed105464c47baccb545eecc6254,
title = "Intravenous administration of lentiviral vectors expressing hyperfunctional factor IX converts severe into mild hemophilia B in a canine model",
abstract = "Lentiviral vectors (LVs) are attractive vehicles for liverdirectedgene therapy by virtue of their ability to stably integratein the genome of target cells and the lack of pre-existingimmunity against vector components in most humans. Over thepast years, we have developed a LV platform that can achievestable transgene expression in the liver and establish correctionof hemophilia in mouse models upon systemic administration.This LV is designed to stringently target transgene expression tohepatocytes through transcriptional and microRNA-mediatedregulation. We then investigated the efficacy and safety ofportal vein administration of LVs expressing wild-type, codonoptimized(c.o.) or c.o. hyperfunctional canine factor IX (cFIX)in a canine model of hemophilia B. We observed long-termstable reconstitution of cFIX activity up to 1% of normal andsignificant amelioration of the clinical phenotype in 3 treateddogs (10 years cumulative follow up). In the perspective ofclinical translation and to increase therapeutic efficacy, we nexttreated a hemophilia B dog by peripheral vein administration ofLVs expressing the c.o. hyperfunctional cFIX at a 5-fold higherdose than those previously administered. At the current followup(6 months after gene therapy) cFIX activity is 7–8% ofnormal, suggesting comparable efficacy of LV by both portaland peripheral vein administration Treatment of more hemophiliaB dogs is underway to extend these results. Overall ourstudies position LV-mediated liver gene therapy for further preclinicaldevelopment and clinical translation. LVs may thuscomplement other available vectors for liver gene therapy ofhemophilia.",
keywords = "gene therapy, hemophilia B, hyperfunctional factor IX ",
author = "A. Cantore and M. Milani and T. Liu and {Della Valle}, P. and A. D'Angelo and T. VandenDriessche and M. Chuah and H. Jiang and T. Nichols and L. Naldini",
year = "2015",
month = oct,
day = "1",
language = "English",
volume = "26",
pages = "A30--A30",
journal = "Human Gene Therapy",
issn = "1043-0342",
publisher = "Mary Ann Liebert",
number = "10",
note = "Collaborative Congress of the European-Society-of-Gene-and-Cell-Therapy (ESGCT) and Finnish-Society-of-Gene-Therapy (FSGT) ; Conference date: 17-09-2015 Through 20-09-2015",
}