title: New approaches to gene and cell therapy for hemophilia.
abstract: Hemophilia is considered suitable for gene therapy because it is caused by a single gene abnormality, and therapeutic coagulation factor levels may vary across a broad range. Recent success of hemophilia B gene therapy with an adeno-associated virus (AAV) vector in a clinical trial showed the real prospect that, through gene therapy, a cure for hemophilia may become a reality. However, AAV-mediated gene therapy is not applicable to patients with hemophilia A at present, and neutralizing antibodies against AAV reduce the efficacy of AAV-mediated strategies. Because patients that benefit from AAV treatment (hemophilia B without neutralizing antibodies) are estimated to represent only 15% of total patients with hemophilia, the development of basic technologies for hemophilia A and those that result in higher therapeutic effects are critical. In this review, we present an outline of gene therapy methods for hemophilia, including the transition of technical developments thus far and our novel techniques.
authors.affiliation: Research Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ohmori
authors.affiliation: Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Mizukami
authors.affiliation: The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ozawa
authors.affiliation: Research Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sakata
authors.affiliation: Research Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.|Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.|Translational Systems Biology and Medicine Initiative, The University of Tokyo, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nishimura
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000235:genetics; D000229:Dependovirus / Q000235:genetics; D018014:Gene Transfer Techniques; D020022:Genetic Predisposition to Disease; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006467:Hemophilia A / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D006470:Hemorrhage / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D006801:Humans; D010641:Phenotype
keywords: cell therapy; gene therapy; genetic; hemophilia; vectors; viruses, adeno‐associated