Introduction
Over the past few years, multiple human gene therapy trials have
successfully achieved hemostatic levels of factors VIII and IX using
recombinant adeno-associated virus (rAAV) vectors.1,2As a culmination of decades of work, rAAV vectors are now receiving
regulatory approval for treatment of both hemophilia A and B.
Unfortunately, over the past few years, data has emerged that now calls
into question the wisdom of using rAAV vectors to treat hemophilia A and
B. This manuscript will review current treatments of hemophilia,
benefits of gene therapy, and the risks of gene therapy. Although other
vectors are in development, since rAAV is the principal vector used for
gene therapy in hemophilia, this manuscript will focus on rAAV toxicity.
At a minimum, a reassessment of the risk/benefit estimate before
routinely administering rAAV vectors to treat hemophilia seems prudent.