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