Oral Nonviral Gene Delivery for Chronic Protein Replacement Therapy

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). Prot...

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Bibliographic Details
Published in:Advanced science 2018-08, Vol.5 (8), p.1701079-n/a
Main Authors: 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.
Format: Article
Language:English
Subjects:
chronic protein replacement therapy
Deoxyribonucleic acid
Diabetes
diabetes mellitus
DNA
Efficiency
Fasting
Gene expression
gene therapy
Glucose
Insulin
Liver
nonviral vectors
oral delivery
Physiology
Spectrum analysis
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Summary: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. A nonviral vector is synthesized for the oral delivery of an insulin plasmid. By protecting the plasmid from gastric acidic degradation and facilitating transport across the gut epithelium, the gene delivery system can achieve sustained blood‐glucose lowering effects in diabetic mice, following repeated oral administrations. The findings suggest this new nonviral gene delivery system is applicable for chronic protein replacement therapy.
ISSN:2198-3844
2198-3844
DOI:10.1002/advs.201701079