期刊
NANO LETTERS
卷 21, 期 11, 页码 4666-4675出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.1c00832
关键词
oral delivery; gene therapy; diabetes; glucagon-like peptide 1; bile acids; protein replacement therapy
类别
资金
- National Research Foundation (NRF) - Korean government [2018R1D1A1A09083269, 2019R1A4A1024116, 2020R1I1A1A01058267, 2021R1A6A1A03046418]
- National Research Foundation of Korea [2021R1A6A1A03046418, 2020R1I1A1A01058267, 2018R1D1A1A09083269] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
A novel gene delivery nanoparticle has been developed in this study, which can protect, transport, and express therapeutic genes effectively through oral administration, showing promising therapeutic effects in diabetes animal models and monkeys.
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.
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