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Sci Rep. 2020 Jan 21;10(1):864. doi: 10.1038/s41598-020-57893-z.

Capsid-specific removal of circulating antibodies to adeno-associated virus vectors.

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Genethon and INSERM U951, 1 rue de l'internationale, 91000, Evry, France.
Atlantic Gene Therapies, Centre de Boisbonne, ONIRIS, La Chantrerie, BP 40706, 44307, Nantes, France.
Institute of Myology, Sorbonne University and INSERM U974, 105 boulevard de l'Hopital, 75013, Paris, France.
CEA, Université Paris-Sud 11, INSERM U1184, Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, Fontenay-aux-Roses, 92265, France.
Assistance Publique-Hôpitaux de Paris, 75013, Paris, France.
Genethon and INSERM U951, 1 rue de l'internationale, 91000, Evry, France.


Neutralizing antibodies directed against adeno-associated virus (AAV) are commonly found in humans. In seropositive subjects, vector administration is not feasible as antibodies neutralize AAV vectors even at low titers. Consequently, a relatively large proportion of humans is excluded from enrollment in clinical trials and, similarly, vector redosing is not feasible because of development of high-titer antibodies following AAV vector administration. Plasmapheresis has been proposed as strategy to remove anti-AAV antibodies from the bloodstream. Although safe and relatively effective, the technology has some limitations mainly related to the nonspecific removal of all circulating IgG. Here we developed an AAV-specific plasmapheresis column which was shown to efficiently and selectively deplete anti-AAV antibodies without depleting the total immunoglobulin pool from plasma. We showed the nearly complete removal of anti-AAV antibodies from high titer purified human IgG pools and plasma samples, decreasing titers to levels that allow AAV vector administration in mice. These results provide proof-of-concept of a method for the AAV-specific depletion of neutralizing antibodies in the setting of in vivo gene transfer.

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