Abstract

Efficient nonviral oral gene delivery offers an attractive modality for chronic protein replacement therapy. Herein, the oral delivery of insulin gene is reported by a nonviral vector comprising a copolymer with a high degree of substitution of branched polyethylenimine on chitosan (CS-g-bPEI). Protecting the plasmid from gastric acidic degradation and facilitating transport across the gut epithelium, the CS-g-bPEI/insulin plasmid DNA nanoparticles (NPs) can achieve systemic transgene expression for days. A single dose of orally administered NPs (600 µg plasmid insulin (pINS)) to diabetic mice can protect the animals from hyperglycemia for more than 10 d. Three repeated administrations spaced over a 10 d interval produce similar glucose-lowering results with no hepatotoxicity detected. Positron-emission-tomography and computed-tomography images also confirm the glucose utilization by muscle cells. While this work suggests the feasibility of basal therapy for diabetes mellitus, its significance lies in the demonstration of a nonviral oral gene delivery system that can impact chronic protein replacement therapy and DNA vaccination.

Original languageEnglish
Article number1701079
JournalAdvanced Science
Volume5
Issue number8
DOIs
Publication statusPublished - Aug 1 2018

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Keywords

  • chronic protein replacement therapy
  • diabetes mellitus
  • gene therapy
  • nonviral vectors
  • oral delivery

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Chemical Engineering(all)
  • Materials Science(all)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Engineering(all)
  • Physics and Astronomy(all)

Cite this

Lin, P. Y., Chiu, Y. L., Huang, J. H., Chuang, E. Y., Mi, F. L., Lin, K. J., Juang, J. H., Sung, H. W., & Leong, K. W. (2018). Oral Nonviral Gene Delivery for Chronic Protein Replacement Therapy. Advanced Science, 5(8), [1701079]. https://doi.org/10.1002/advs.201701079