How to optimise gene therapy by AAV in humans, from an immunological point of view?

At a time of unprecedented development of AAV-based gene therapies in neuromuscular disease, and in view of the difficulties encountered during therapeutic trials and in a real-life setting, German researchers have reviewed possible ways of improving the coexistence of humans with AAV« adeno-associated virus » , ou virus adéno-associé est un petit virus à ADN simple brin. Il fait partie de la famille des Parvoviridae et appartient au genre des Dependovirus. La particule virale est constituée d’un brin d’ADN de polarité positive ou négative protégé par une capside. La taille moyenne d’une particule d’AAV et de 18 à 22 nm. Les AAV sont les seuls parvovirus non autonomes. Lorsqu’on emploie « rAAV » , il s’agit du virus AAV recombinant, c’est-à-dire qu’il a été modifié pour devenir un vecteur (et n’est donc plus virulent). itself. Among the many avenues mentioned, one should note the benefit of:

• targeting organs that are more immunotolerant to the AAVs, such as the brain, the liver and the eyes;
• inducing immunotolerance using reprogrammed regulatory T cells or medicines;
• using, more broadly, immunosuppressants to prevent any undesirable immune reaction;
• getting rid of neutralising antibodies against AAV;
• improving AAV itself.

Adeno-Associated Viruses (AAV) and Host Immunity – A Race Between the Hare and the Hedgehog. Rapti K, Grimm D. Front Immunol. 2021 Oct 29;12:753467.