Federico Mingozzi: Assessing and modulating immune responses to AAV vectors in humans скачать в хорошем качестве

Federico Mingozzi: Assessing and modulating immune responses to AAV vectors in humans

Recombinant adeno-associated virus (AAV) vectors have been successfully used in humans to treat inherited diseases such as congenital blindness and hemophilia B. Despite their excellent safety and tolerability profile, immune responses directed against the AAV vector capsid represent an important safety and efficacy concern in clinical gene transfer trials with this therapeutic platform. Because exposure to the wild-type AAV happens early in life, humans develop both anti-AAV antibodies and memory T cells specific to AAV capsid epitopes. Anti-AAV neutralizing antibodies can completely clear AAV vector from the circulation, resulting in lack of efficacy. Cellular immunity to AAV vectors may interfere with the duration of therapeutic efficacy following gene transfer. One of the challenges in the study of these responses is their correlation with the clinical end points, which is not always straightforward. Nonetheless, the field has done enormous progress towards identifying the determinants of AAV vectors immunogenicity and developing strategies to circumvent these limitations, getting closer to the goal of achieving sustained, long-term correction of disease phenotype following in vivo gene transfer.