한빛사논문
- 조회557
Hien Bao Dieu Thaia,†, Kyoung-Ran Kima,†, Kyung Tae Hongb, Taras Voitsitskyib, Jun-Seok Leeb,c, Chengde Maod, and Dae-Ro Ahna,b,*
aCenter for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Korea
bDivision of Biomedical Science and Technology, KIST School, Korea University of Science and Technology (UST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Korea
cMolecular Recognition Research Center, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Korea
dDepartment of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
†These authors contributed equally to this work
*Corresponding author
Abstract
A proper intracellular delivery method with target tissue specificity is critical to utilize the full potential of therapeutic molecules including siRNAs while minimizing their side effects. Herein, we prepare four small-sized DNA tetrahedrons (sTds) by self-assembly of different sugar backbone-modified oligonucleotides and screened them to develop a platform for kidney-targeted cytosolic delivery of siRNA. An in vivo biodistribution study revealed the kidney-specific accumulation of mirror DNA tetrahedron (L-sTd). Low opsonization of L-sTd in serum appeared to avoid liver clearance and keep its size small enough to be filtered through the glomerular basement membrane (GBM). After GBM filtration, L-sTd could be delivered into tubular cells by endocytosis. The kidney preference and the tubular cell uptake property of the mirror DNA nanostructure could be successfully harnessed for kidney-targeted intracellular delivery of p53 siRNA to treat acute kidney injury (AKI) in mice. Therefore, L-sTd could be a promising platform for kidney-targeted cytosolic delivery of siRNA to treat renal diseases.
논문정보
- Research article
- 2020년 11월 (BRIC 등록일 2020-11-30)
- 국내(교신)+국외 연구진
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