Targeting Sinusoial Endothelium
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

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)

LV-pF8-FVIII Corrected FVIII Level in B6/129-HA Mice is Treg Dependent

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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Supported by educational grants from Bayer, BioMarin, CSL Behring, Freeline Therapeutics Limited, Pfizer Inc., Spark Therapeutics, and uniQure, Inc.

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