title: Adeno-associated viral vectors for the treatment of hemophilia.
abstract: Gene transfer studies for the treatment of hemophilia began more than two decades ago. A large body of pre-clinical work evaluated a variety of vectors and target tissues, but by the start of the new millennium it became evident that adeno-associated viral (AAV)-mediated gene transfer to the liver held great promise as a therapeutic tool. The transition to the clinical arena uncovered a number of unforeseen challenges, mainly in the form of a human-specific immune response against the vector that poses a significant limitation in the application of this technology. While the full nature of this response has not been elucidated, long-term expression of therapeutic levels of factor IX is already a reality for a small number of patients. Extending this success to a greater number of hemophilia B patients remains a major goal of the field, as well as translating this strategy to clinical therapy for hemophilia A. This review summarizes the progress of AAV-mediated gene therapy for the hemophilias, along with its upcoming prospects and challenges.
authors.affiliation: Spark Therapeutics, Inc., 3737 Market St, Suite 1300, Philadelphia, PA, USA kathy.high@sparktx.com.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: High
authors.affiliation: Spark Therapeutics, Inc., 3737 Market St, Suite 1300, Philadelphia, PA, USA.
authors.forename: Xavier M
authors.initials: XM
authors.lastname: Anguela
mesh_terms: D000229:Dependovirus / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors; D006467:Hemophilia A / Q000628:therapy*; D002836:Hemophilia B / Q000628:therapy*; D006801:Humans