Abstract
Hemophilia is a monogenic disease with robust clinicolaboratory correlations of severity.
These attributes coupled with the availability of experimental animal models have
made it an attractive model for gene therapy. The road from animal models to human
clinical studies has heralded significant successes, but major issues concerning a
previous immunity against adeno-associated virus and transgene optimization remain
to be fully resolved. Despite significant advances in gene therapy application, many
questions remain pertaining to its use in specific populations such as those with
factor inhibitors, those with underlying liver disease, and pediatric patients. Here,
the authors provide an update on viral vector and transgene improvements, review the
results of recently published gene therapy clinical trials for hemophilia, and discuss
the main challenges facing investigators in the field.
Keywords
hemophilia - factor VIII - factor IX - gene therapy - AAV vector