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Related Concept Videos

siRNA - Small Interfering RNAs02:30

siRNA - Small Interfering RNAs

Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
RNA Interference01:23

RNA Interference

RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...

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Related Experiment Video

Updated: Jun 20, 2026

Long-term Silencing of Intersectin-1s in Mouse Lungs by Repeated Delivery of a Specific siRNA via Cationic Liposomes. Evaluation of Knockdown Effects by Electron Microscopy
15:55

Long-term Silencing of Intersectin-1s in Mouse Lungs by Repeated Delivery of a Specific siRNA via Cationic Liposomes. Evaluation of Knockdown Effects by Electron Microscopy

Published on: June 21, 2013

A ROS-Responsive DNA Nanodevice for Targeted Cytosolic siRNA Delivery in Metabolic Dysfunction-Associated

Qi Wang1,2, Beibei Zhang1,3, Yuang Wang1,2

  • 1State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing, Jiangsu 210023, China.

Journal of the American Chemical Society
|June 19, 2026
PubMed
Summary
This summary is machine-generated.

Researchers developed a novel DNA origami nanodevice (TRIO) for targeted delivery of small interfering RNA (siRNA) to treat metabolic dysfunction-associated steatohepatitis (MASH). This approach bypasses endosomes, reducing inflammation and effectively treating liver disease in mice.

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Porous Silicon Microparticles for Delivery of siRNA Therapeutics

Published on: January 15, 2015

Area of Science:

  • Biotechnology
  • Nanomedicine
  • Hepatology

Background:

  • Metabolic dysfunction-associated steatohepatitis (MASH) involves complex metabolic, inflammatory, and fibrogenic pathways, with current treatments being insufficient.
  • Small interfering RNA (siRNA) therapeutics show promise but are limited by endosomal escape issues, potentially causing inflammation.
  • Targeted delivery of siRNA to hepatocytes, independent of endosomes, is crucial for effective MASH intervention.

Purpose of the Study:

  • To develop a novel DNA origami nanodevice for endosome-independent, hepatocyte-selective cytosolic delivery of siRNA.
  • To create an inflammation-responsive system for MASH treatment by targeting specific molecular drivers.
  • To evaluate the therapeutic efficacy of the nanodevice in cellular and murine models of MASH.

Main Methods:

  • Designed TRIO (Thiol-mediated siRNA delivery by Inflammation-responsive DNA Origami), a DNA nanodevice with a steric gating strategy for thiol-mediated uptake.
  • Functionalized TRIO with N-acetylgalactosamine (GalNAc) ligands for enhanced hepatocyte targeting.
  • Utilized reactive oxygen species (ROS) in inflamed hepatic environments to trigger nanodevice reconfiguration and siRNA release.
  • Assessed the downregulation of MASH-related genes (HSD17B13, TAZ) and evaluated therapeutic effects in cellular and murine MASH models.

Main Results:

  • TRIO demonstrated efficient, endosome-independent cytosolic delivery of siRNA to hepatocytes.
  • The nanodevice successfully downregulated key MASH drivers (HSD17B13, TAZ), attenuating cellular lipid dysregulation, inflammation, and fibrosis.
  • In a murine MASH model, TRIO ameliorated hepatic steatosis, inflammation, and fibrosis, accelerating disease resolution.
  • The steric gating strategy proved effective for inflammation-responsive, targeted nucleic acid delivery.

Conclusions:

  • Established a steric gating strategy for targeted cytosolic siRNA delivery, overcoming endosomal escape limitations.
  • Developed an integrated nanodevice system (TRIO) for coordinated MASH intervention.
  • Demonstrated the potential of inflammation-responsive DNA origami nanodevices for treating liver diseases and other conditions requiring targeted nucleic acid therapeutics.