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Related Concept Videos

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...
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...
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.
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Riboswitches01:56

Riboswitches

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Related Experiment Video

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Delivery of Therapeutic siRNA to the CNS Using Cationic and Anionic Liposomes
10:33

Delivery of Therapeutic siRNA to the CNS Using Cationic and Anionic Liposomes

Published on: July 23, 2016

Dicer-labile PEG conjugates for siRNA delivery.

Siew Ching Kow1, Josh McCarroll, David Valade

  • 1School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.

Biomacromolecules
|November 8, 2011
PubMed
Summary

Poly(ethylene glycol) (PEG) conjugated Dicer-substrate small interfering RNA (DsiRNA) show potent gene silencing. PEG-DsiRNA conjugates were less immunogenic, offering a promising strategy for siRNA delivery.

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Last Updated: May 27, 2026

Delivery of Therapeutic siRNA to the CNS Using Cationic and Anionic Liposomes
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Published on: July 23, 2016

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Synthesis, Functionalization, and Characterization of Fusogenic Porous Silicon Nanoparticles for Oligonucleotide Delivery

Published on: April 16, 2019

Area of Science:

  • Biochemistry
  • Molecular Biology
  • RNA Interference

Background:

  • Small interfering RNA (siRNA) therapeutics offer targeted gene silencing.
  • Developing efficient and safe siRNA delivery systems remains a challenge.
  • Poly(ethylene glycol) (PEG) conjugation is a common strategy to improve drug properties.

Purpose of the Study:

  • To investigate a novel siRNA release strategy using PEG-DsiRNA conjugates.
  • To evaluate the efficacy and immunogenicity of PEGylated DsiRNA.
  • To explore the impact of PEG molecular weight on DsiRNA function.

Main Methods:

  • Covalent conjugation of thiol-modified DsiRNAs to PEG (2, 10, 20 kg/mol) via Michael addition.
  • Assessing DsiRNA cleavage by recombinant human Dicer using gel electrophoresis.
  • Evaluating gene silencing activity in eGFP-expressing SH-EP cells at mRNA and protein levels.
  • Measuring immunogenicity using an immune stimulation assay on human peripheral blood mononuclear cells.

Main Results:

  • DsiRNA conjugates with 2 and 10 kg/mol PEG were efficiently cleaved by Dicer to release siRNA.
  • PEG-DsiRNA conjugates (2 and 10 kg/mol PEG on 3'-sense strand) demonstrated potent gene silencing in vitro.
  • The 10 kg/mol PEG conjugate showed reduced immunogenicity compared to unmodified DsiRNA.

Conclusions:

  • PEGylation of DsiRNA via a stable thioether bond is a viable strategy for siRNA delivery.
  • PEG-DsiRNA conjugates can be efficiently processed by Dicer and retain gene silencing activity.
  • PEGylation can reduce the immunogenicity of DsiRNA, enhancing its therapeutic potential.