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Highlights From NHF's 16th Workshop on Novel Technologies and Gene Transfer for Hemophilia
Targeting Sinusoial Endothelium
Antonia Follenzi, MD, PhD
University of Piemonte Orientale
Novara, Italy
Key Data Points
- pF8 Promoter Drives GFP Expression in LSECs
- LV-pF8-FVIII Corrected FVIII Level in B6/129-HA Mice is Treg Dependent
The natural FVIII promoter, pF8, drives GFP expression in liver sinusoidal endothelial cells (LSECs). Immunofluorescence analysis of liver of C57BL/6 hemophilia A (HA) mice, 1 and 6 months after injection of the lentiviral vector LV.pF8.GFP. (DAPI, 4′,6-diamidino-2-phenylindole; GFP, green fluorescent protein; Lyve-1, lymphatic vessel endothelial receptor 1, a marker for LSECs)
To summarize this series of studies, immunosuppression with minimal reduction in Treg cells is optimal for ensuring liver-mediated immune tolerance to FIX transgene expression. In NHPs, pretreatment with MMF and rapamycin, followed by delayed administration of rATG was able to provide sustained immune tolerance whereas rATG or daclizumab administered at the time of vector infusion was not.
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