nl1c00832_si_001.pdf (2.25 MB)
Plasmid DNA Nanoparticles for Nonviral Oral Gene Therapy
journal contribution
posted 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 LeeHerein,
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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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