Gene transfer to hemophilia A mice via oral delivery of FVIII-chitosan nanoparticles.

Published

Journal Article

Effective oral delivery of a non-viral gene carrier would represent a novel and attractive strategy for therapeutic gene transfer. To evaluate the potential of this approach, we studied the oral gene delivery efficacy of DNA polyplexes composed of chitosan and Factor VIII DNA. Transgene DNA was detected in both local and systemic tissues following oral administration of the chitosan nanoparticles to hemophilia A mice. Functional factor VIII protein was detected in plasma by chromogenic and thrombin generation assays, reaching a peak level of 2-4% FVIII at day 22 after delivery. In addition, a bleeding challenge one month after DNA administration resulted in phenotypic correction in 13/20 mice given 250-600 microg of FVIII DNA in chitosan nanoparticles, compared to 1/13 mice given naked FVIII DNA and 0/6 untreated mice. While further optimization would be required to render this type of delivery system practical for hemophilia A gene therapy, the findings suggest the feasibility of oral, non-viral delivery for gene medicine applications.

Full Text

Cited Authors

  • Bowman, K; Sarkar, R; Raut, S; Leong, KW

Published Date

  • December 2008

Published In

Volume / Issue

  • 132 / 3

Start / End Page

  • 252 - 259

PubMed ID

  • 18634839

Pubmed Central ID

  • 18634839

Electronic International Standard Serial Number (EISSN)

  • 1873-4995

International Standard Serial Number (ISSN)

  • 0168-3659

Digital Object Identifier (DOI)

  • 10.1016/j.jconrel.2008.06.019

Language

  • eng