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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...
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Updated: Oct 13, 2025

Polyethyleneimine-coated Iron Oxide Nanoparticles as a Vehicle for the Delivery of Small Interfering RNA to Macrophages In Vitro and In Vivo
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Efficient and safe small RNA delivery to macrophage using peptide-based nanocomplex.

Yeong Chae Ryu1, Yoo Eun Lee1, Byeong Hee Hwang1,2

  • 1Department of Bioengineering and Nano-bioengineering, Incheon National University, Incheon, Korea.

Biotechnology and Bioengineering
|November 11, 2021
PubMed
Summary

Researchers developed a novel S-R11 fusion peptide for delivering small interfering RNA (siRNA) and short hairpin RNA (shRNA) into immune cells. This peptide forms a nanocomplex, improving gene silencing and offering a promising gene therapy delivery system.

Keywords:
gene silencingnanocomplexpeptideself-assemblysmall RNA

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Area of Science:

  • Biotechnology
  • Molecular Biology
  • Gene Therapy

Background:

  • RNA interference (RNAi) is a gene-silencing mechanism with therapeutic potential for various diseases.
  • Efficient and safe delivery of small RNAs (siRNA, shRNA) is crucial for successful RNAi.
  • Immune cells present a significant challenge for conventional gene delivery methods.

Purpose of the Study:

  • To develop a novel peptide-based delivery system for small RNAs into immune cells.
  • To evaluate the efficacy and safety of the S-R11 fusion peptide for gene delivery.

Main Methods:

  • An S-R11 fusion peptide (SPACE peptide conjugated with poly-arginine) was synthesized.
  • The peptide was used to form self-assembling nanocomplexes with small RNAs.
  • Nanocomplexes were tested for delivery efficiency in RAW 264.7 macrophage cells.
  • Gene silencing efficacy and cell viability were assessed.

Main Results:

  • The S-R11 peptide formed stable nanocomplexes with small RNAs via electrostatic attraction and hydrogen bonding.
  • The nanocomplex demonstrated a 5.3-fold higher permeation efficiency compared to Lipofectamine™ 2000 in macrophage cells.
  • A 66.2% target gene silencing effect was achieved in poly (I:C)-activated cells.
  • The fusion peptide exhibited good cell viability, even at high concentrations.

Conclusions:

  • The S-R11 fusion peptide-based nanocomplex is an effective system for delivering small RNAs into immune cells.
  • This system overcomes challenges associated with gene therapy delivery to immune cells.
  • It holds promise as a novel gene delivery vector for future therapeutic applications.