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

JOURNAL OF CONTROLLED RELEASE

卷:132

Article

Bowman, Katherine²  Sarkar, Rita³  Raut, Sanj⁴  Leong, Kam W.^1,5 

[1] Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA

[2] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA

[3] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA

[4] Natl Inst Biol Stand & Controls, Div Haematol, Potters Bar, Herts, England

[5] Duke Univ, Dept Surg, Durham, NC 27708 USA

关键词: Non-viral gene delivery;    Hemophilia therapy;    Chitosan;    Oral delivery;    Gene medicine;   

DOI  :  10.1016/j.jconrel.2008.06.019

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free