No CpGs for AAVs?

Abstract

In this issue of Blood, Konkle et al report that 7 of 8 participants in a phase 1/2 trial of adeno-associated virus (AAV) vector (BAX335) for factor IX (FIX)-Padua gene transfer in patients with hemophilia B did not maintain expression despite steroid intervention, which the authors hypothesize is a result of the innate immune stimulatory effect of CpG motifs enriched within their vector cassette. Their study demonstrates that the cellular immune response to AAV vectors does not always respond to steroids and provides insight into mechanisms that may contribute to the AAV immune response with implications for the future design of AAV vectors.