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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...
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...

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Updated: May 10, 2026

Porous Silicon Microparticles for Delivery of siRNA Therapeutics
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Enhancing WRAP-Based Nanoparticles for Small Interfering Ribonucleic Acid Delivery in pH-Sensitive Environments.

Giulia Di Gregorio1, Coélio Vallée2, Karidia Konate1

  • 1PhyMedExp, University of Montpellier, INSERM, CNRS, 371 Av. Doyen Giraud, 34295, Montpellier, France.

Chemmedchem
|March 14, 2025
PubMed
Summary
This summary is machine-generated.

Researchers developed pH-sensitive nanoparticles using WRAP5 peptides and siRNA for targeted delivery in myocardial infarction. These nanoparticles effectively deliver therapeutic siRNA to injured heart cells, inhibiting apoptosis.

Keywords:
acylhydrazonespH sensitivepeptide‐based nanoparticlessmall interfering ribonucleic acid deliverytargeting

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Area of Science:

  • Biotechnology
  • Nanomedicine
  • Cardiovascular Research

Background:

  • Small interfering RNAs (siRNA) are potent therapeutic agents but require effective delivery systems.
  • Existing siRNA delivery systems include lipid- or peptide-based nanoparticles.
  • Acute myocardial infarction involves ischemic heart tissue with a characteristic pH drop.

Purpose of the Study:

  • To optimize WRAP5-based nanoparticles for pH-sensitive siRNA delivery in myocardial infarction.
  • To investigate targeted delivery of siRNA to inhibit apoptosis in ischemic heart tissue.
  • To evaluate the efficacy of PEGylated WRAP5 nanoparticles in a pH-dependent manner.

Main Methods:

  • Conception and validation of WRAP5 peptide-forming nanoparticles with siRNA.
  • Optimization of nanoparticles using pH-sensitive acyl hydrazone linkers to graft polyethylene glycol (PEG).
  • Proof-of-concept study using siRNA to silence the Fas-associated death domain (FADD) protein in human vascular endothelial cells and hiPSC-derived cardiomyocytes at pH 5.

Main Results:

  • PEGylated WRAP5 nanoparticles demonstrated pH-sensitive siRNA delivery.
  • Specific FADD knockdown was achieved at pH 5 using optimized nanoparticles, unlike naked nanoparticles.
  • The system showed targeted delivery and inhibition of apoptosis-related protein FADD.

Conclusions:

  • Optimized WRAP5-based nanoparticles offer a novel therapeutic tool for myocardial infarction.
  • pH-sensitive nanoparticle design facilitates targeted siRNA delivery to injured cells.
  • This approach can inhibit reperfusion-induced apoptosis and enhance local therapeutic delivery.