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Efficient and safe correction of hemophilia A by lentiviral vector-transduced BOECs in an implantable device

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journal contribution
posted on 08.11.2021, 11:17 by Cristina Olgasi, Chiara Borsotti, Simone Merlin, Thorsten Bergmann, Patrick Bittorf, Adeolu Badi Adewoye, Nicholas Wragg, Kelcey Patterson, Andrea Calabria, Fabrizio Benedicenti, Alessia Cucci, Alessandra Borchiellini, Berardino Pollio, Eugenio Montini, Delfina M Mazzuca, Martin Zierau, Alexandra StolzingAlexandra Stolzing, Philip M Toleikis, Joris Braspenning, Antonia Follenzi
Hemophilia A (HA) is a rare bleeding disorder caused by deficiency/dysfunction of the FVIII protein. As current therapies based on frequent FVIII infusions are not a definitive cure, long-term expression of FVIII in endothelial cells through lentiviral vector (LV)-mediated gene transfer holds the promise of a one-time treatment. Thus, here we sought to determine whether LV-corrected blood outgrowth endothelial cells (BOECs) implanted through a prevascularized medical device (Cell Pouch™) would rescue the bleeding phenotype of HA mice. To this end, BOECs from HA patients and healthy donors were isolated, expanded and transduced with an LV carrying FVIII driven by an endothelial-specific promoter employing GMP-like procedures. FVIII-corrected HA-BOECs were either directly transplanted into the peritoneal cavity or injected into a Cell Pouch™ implanted subcutaneously in NSG-HA mice. In both cases, FVIII secretion sufficient to improve the mouse bleeding phenotype. Indeed, FVIII-corrected HA-BOECs reached a relatively short-term clinically relevant engraftment being detected up to 16 weeks after transplantation, and their genomic integration profile did not show enrichment for oncogenes, confirming the process safety. Overall, this is the first pre-clinical study showing the safety and feasibility of transplantation of GMP-like produced LV-corrected BOECs within an implantable device for the long-term treatment of HA.


European Union's Horizon 2020 research and innovation program under grant agreement HemAcure No. 667421

Telethon grant No. GGP19201

Vanguard grant No. 874700

Università del Piemonte Orientale (FAR 2017)

Fondazione Carliplo grant No 2018-0253

Italian Minister of Health “Ricerca 523 Sanitaria finalizzata” Giovani Ricercatori Grant No 2018-12366399



  • Mechanical, Electrical and Manufacturing Engineering

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Molecular Therapy - Methods & Clinical Development






Elsevier BV


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This is an Open Access Article. It is published by Elsevier under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0). Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/

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Prof Alexandra Stolzing. Deposit date: 5 November 2021

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