nl1c00832_si_001.pdf (2.25 MB)
Plasmid DNA Nanoparticles for Nonviral Oral Gene Therapy
journal contributionposted on 2021-05-24, 22:03 authored by S. M. Shatil Shahriar, Jeong Man An, Mohammad Nazmul Hasan, Sachin S. Surwase, Yeu-Chun Kim, Dong Yun Lee, Sungpil Cho, Yong-kyu Lee
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.
gene delivery nanoparticle exhibitsdiabetes mouse modelsbile acid-specific transporteroptimized dosage formenterohepatic recycling systemweight gainnonfast blood glucose levels1Cvivo studiespDNA NPsfood uptake behaviorstage diabetes conditionsNonviral Oral Gene Therapy Herein14 daysbile acid-inspired20 weeks7 daysPlasmid DNA Nanoparticlesgene expression kineticsgene delivery platformtreatment experience