Among gene therapy techniques currently under investigation, several have been
successful in mice with hemophilia. In principle, by supplementing the missing genetic
information – the factor VIII (FVIII) gene – scientists should be able to produce healthy
levels of FVIII. Numerous gene therapy approaches have used viruses as a means of
delivering the missing FVIII gene. The major challenge has been to find ways of
bypassing or deactivating the natural immune response to these experimental treatments.
Carol H. Miao, PhD, research assistant professor in pediatrics at the University of
Washington and a past recipient of the National Hemophilia Foundation’s Career
Development Award, has been studying nonviral approaches to gene therapy to treat
hemophilia A. In a recent study,* Miao and colleagues report developing a successful
gene therapy technique to treat hemophilia A. Their technique entails first injecting
naked DNA, genetic information that is not contained or attached to a particular vehicle,
directly into the livers of mice with hemophilia. This is then followed by a regimen of
various immunosuppressants, drugs that help control the immune response.
Miao and colleagues identified a combination of two types of immunosuppressants that
produced the best blockade to the immune response against FVIII. (An attempt at gene
therapy using only one type of immunosuppressant was not effective.) Miao and
colleagues discovered that manipulation of the immune response after the injection of
naked DNA produced long-term FVIII immune tolerance in hemophilia A mice. The
study may ultimately provide valuable insight into future gene therapy techniques for
people with hemophilia.
*Miao, Carol H., et al. “Immunomodulation of Transgene Responses Following Naked
DNA Transfer of Human Factor VIII into Hemophilia A Mice.” Blood. 2006;