Kidney-Targeted Cytosolic Delivery of siRNA Using a Small-Sized Mirror DNA Tetrahedron for Enhanced Potency

Hien Bao Dieu Thai, Kyoung Ran Kim, Kyung Tae Hong, Taras Voitsitskyi, Jun Seok Lee, Chengde Mao, Dae Ro Ahn

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2250-2258
Number of pages9
JournalACS Central Science
Issue number12
Publication statusPublished - 2020 Dec 23
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by intramural grants of KIST, the Pioneer Research Center Program (2014M3C1A3054141) and National Research Foundation of Korea grant funded by the Korea government (MSIT) (2020R1A2C2008213). It was also supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF funded by the Korean government (MSIT) (2020M3E5E2037598).

Publisher Copyright:
© 2020 American Chemical Society.

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)


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