- Bowman, K. and Sarkar, R. and Raut, S. and Leong, K. W., Gene transfer to hemophilia A mice via oral delivery of FVIII-chitosan nanoparticles,
Journal of Controlled Release, vol. 132 no. 3
pp. 252-259 .
(last updated on 2010/06/11)
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 mu g 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. (C) 2008 Elsevier B.V. All rights reserved.
non-viral gene delivery hemophilia therapy chitosan oral delivery gene medicine human-factor-viii DNA nanoparticles particle-size therapy expression vectors nanospheres derivatives efficiency mutations