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

Fingerprint

insulin
plasmids
Insulin
genes
therapy
delivery
Plasmids
Genes
proteins
Proteins
glucose
Nanoparticles
Glucose
DNA
hyperglycemia
deoxyribonucleic acid
tomography
diabetes mellitus
Polyethyleneimine
muscle cells

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

Oral Nonviral Gene Delivery for Chronic Protein Replacement Therapy. / Lin, Po Yen; Chiu, Ya Ling; Huang, Jing Huei; Chuang, Er Yuan; Mi, Fwu Long; Lin, Kun Ju; Juang, Jyuhn Huarng; Sung, Hsing Wen; Leong, Kam W.

In: Advanced Science, Vol. 5, No. 8, 1701079, 01.08.2018.

Research output: Contribution to journalArticle

Lin, PY, Chiu, YL, Huang, JH, Chuang, EY, Mi, FL, Lin, KJ, Juang, JH, Sung, HW & Leong, KW 2018, 'Oral Nonviral Gene Delivery for Chronic Protein Replacement Therapy', Advanced Science, vol. 5, no. 8, 1701079. https://doi.org/10.1002/advs.201701079
Lin, Po Yen ; Chiu, Ya Ling ; Huang, Jing Huei ; Chuang, Er Yuan ; Mi, Fwu Long ; Lin, Kun Ju ; Juang, Jyuhn Huarng ; Sung, Hsing Wen ; Leong, Kam W. / Oral Nonviral Gene Delivery for Chronic Protein Replacement Therapy. In: Advanced Science. 2018 ; Vol. 5, No. 8.
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