Stabilin-2 Promoter Modulates the Immune Response to FVIII After Lentiviral Vector Delivery in Hemophilic Mice

Highlights From the ASGCT 25th Annual Meeting

Stabilin-2 Promoter Modulates the Immune Response to FVIII After Lentiviral Vector Delivery in Hemophilic Mice

Presented by: Antonia Follenzi, MD, PhD, University of Piemonte Orientale, Novara, Italy

Antonia Follenzi¹, Ester Borroni¹, Roberta A. Cirsmaru¹, Paolo E. Di Simone¹, Rosella Famà¹, Valentina Bruscaggin¹, Simone Merlin¹, Brian D. Brown², Chiara Borsotti¹

¹Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
²Department of Health Sciences, Mount Sinai School of Medicine, New York, New York

Key Data Points

Stablin-2 (STAB2) Promoter Directs Expression in LSECs
STAB2 Promoter Directs Expression of LV.pSTAB2.FVIII in Hemophilia A Mice

Stablin-2 (STAB2) Promoter Directs Expression in LSECs

STAB2 is a scavenger receptor involved in the clearance of hyaluronan and the vWF-FVIII complex. The receptor is mainly expressed within liver by liver sinusoidal endothelial cells (LSECs). The STAB2 promoter was used to direct GFP expression in LSECs upon lentiviral (LV) delivery. Injection of LV.STAB2-GFP/FVIII vectors into immune-reactive BALB/c mice showed endothelial targeting and long-term maintenance of transgene expression in comparison to the use of PGK, a ubiquitous promoter for which expression was cleared within 2 weeks in injected mice.

STAB2 Promoter Directs Expression of LV.pSTAB2.FVIII in Hemophilia A Mice

STAB2 promoter activity was evaluated further in vivo by injecting LV carrying FVIII transgene in several strains of hemophilic mice followed by assessment of FVIII activity and neutralizing antibodies formation. As shown here, LV delivery of FVIII transgene, driven by the STAB2 promoter, led to FVIII expression mainly in LSECs (left panel) without neutralizing antibodies (right panel) for up to one year.