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Portal Vein Delivery of Viral Vectors for Gene Therapy for Hemophilia

Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1114)

Abstract

The liver is a very complex organ with a large variety of functions, making it an attractive organ for gene replacement therapy. Many genetic disorders can be corrected by delivering gene products directly into the liver using viral vectors. In this chapter, we will describe gene delivery via portal vein administration in mice and dogs to correct the blood coagulation disorder hemophilia B. Although there are multiple delivery routes for both viral and non-viral vectors in animals, portal vein administration delivers vectors directly and efficiently into the liver. Complete correction of murine hemophilia B and multi-year near-correction of canine hemophilia B have been achieved following portal vein delivery of adeno-associated viral (AAV) vectors expressing factor IX from hepatocyte-specific promoters. Peripheral vein injection can lead to increased vector dissemination to off-target organ such as the lung and spleen. Below, we will describe portal vein injection delivery route via laparotomy.

Key words

Liver Gene therapy Portal vein Viral vectors AAV 

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Copyright information

© Springer Science+Business Media, LLC 2014

Authors and Affiliations

  1. 1.Department of PediatricsUniversity of FloridaGainesvilleUSA
  2. 2.Department of MedicineDrexel UniversityPhiladelphiaUSA
  3. 3.Francis Owen Blood Research LaboratoryUniversity of North CarolinaChapel HillUSA

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