Nature Communication: No immunogenicity! Can the spring of AAV mediated gene therapy be far behind?

Detail

Introduction: Recombinant adeno-associated virus (AAV) vectors exhibit promising outcomes on gene therapy with its durable expression in the targeting tissues. Even so, in most cases, AAV immunogenicity still represents a major limitation for its clinical trials. Recently, a research team from Sorbonne Université and INSERM U974 (France) has employed an effective means to avoid AAV immunogenicity, which makes AAV safer and provide reference for its further clinical trial.

This result entitled by “Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration” was published online on Oct 5th in the journal of Nature Communications. In the study, the authors co-administrated a synthetic vaccine particle containing rapamycin (SVP[Rapa]) with AAV vectors. Rapamycin encapsulated particles has been reported to alleviate the immune response when co-dosing with protein therapeutics. This team tactfully applied this combination on AAV mediated gene targeting which reduced anti-capsid humoral and T/B cell-mediated immune response, allowing for successful vector re-administration in mice and nonhuman primates.

Furthermore, Meliani and colleagues explored the underlying mechanism of how rapamycin contained particles reduce AVV immunogenicity. They found depletion of CD25+ T cells could abolish this anti-immunogenicity effects, suggesting a critical role of regulatory T cells in this process.

As a whole, this study discovered an effective means to reduce AAV immunogenicity, which not only ensures the durable expression off AAV in the targeting organ but also allows for re-dosing, providing a powerful strategy to AAV mediated gene therapy.

References
1. Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challenges.
2. Overcoming the host immune response to adeno-associated virus gene delivery vectors: the race between clearance, tolerance, neutralization, and escape.
3. Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration.