Plasmid DNA Nanoparticles for Nonviral Oral Gene Therapy

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Herein, a bile acid-inspired triple padlock oral gene delivery platform is developed, facilitating the protection of the therapeutic gene from gastrointestinal degradation, selective intestinal accumulation through a bile acid-specific transporter, and transportation of pDNA NPs through the enterohepatic recycling system. This nonviral oral gene delivery nanoparticle exhibits excellent gene expression kinetics in in vitro, in vivo, and ex vivo studies. A single oral dose leads to maintaining normoglycemia for up to 7 days in three different diabetes mouse models and 14 days in diabetic monkeys. Also, the optimized dosage form can reduce nonfast blood glucose levels and hemoglobin A1C within a normal range from the last stage diabetes conditions with a reduction of weight gain from changes of food uptake behavior after treatment once weekly for 20 weeks. Taken together, the current findings could improve the current painful treatment experience of diabetics and thus improve their quality of life.
Publisher
AMER CHEMICAL SOC
Issue Date
2021-06
Language
English
Article Type
Article
Citation

NANO LETTERS, v.21, no.11, pp.4666 - 4675

ISSN
1530-6984
DOI
10.1021/acs.nanolett.1c00832
URI
http://hdl.handle.net/10203/286566
Appears in Collection
CBE-Journal Papers(저널논문)
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