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Related Concept Videos

Experimental RNAi02:15

Experimental RNAi

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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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Efficient Gene Knockdown in the Liver via Intrasplenic Injection of Adeno-Associated Virus Serotype 8 (AAV8)-Delivered Small Hairpin RNA
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Efficient Gene Knockdown in the Liver via Intrasplenic Injection of Adeno-Associated Virus Serotype 8 (AAV8)-Delivered Small Hairpin RNA

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Delivering siRNA Compounds During HOPE to Modulate Organ Function: A Proof-of-concept Study in a Rat Liver Transplant

Eliano Bonaccorsi-Riani1,2, Andrew R Gillooly3, Samuele Iesari2,4

  • 1Abdominal Transplant Unit, Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium.

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Small interfering RNA (siRNA) targeting the FAS gene reduced liver ischemia-reperfusion injury (IRI) after static cold storage in a rat liver transplant model. Combining siRNA with hypothermic oxygenated perfusion presented challenges.

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Area of Science:

  • Hepatology
  • Transplantation immunology
  • Molecular biology

Background:

  • Apoptosis exacerbates ischemia-reperfusion injury (IRI), a key limitation in liver transplantation (LT).
  • Machine perfusion offers a platform for therapeutic interventions to enhance graft viability.
  • Targeting apoptosis-associated genes during perfusion may mitigate IRI.

Purpose of the Study:

  • To investigate the efficacy of inhibiting the apoptosis-associated gene FAS using small interfering RNA (siRNA) in a rat LT model to alleviate IRI.

Main Methods:

  • FAS siRNA was administered to rat donors before organ procurement and static cold storage (SCS).
  • FAS siRNA was added to the perfusate during ex situ hypothermic oxygenated perfusion (HOPE) after initial SCS.
  • Liver enzyme levels, cytokine profiles, and apoptotic markers were assessed post-LT.

Main Results:

  • SCS with FAS siRNA significantly reduced transaminase levels and pro-inflammatory cytokines 24 hours post-LT.
  • HOPE with FAS siRNA increased anti-inflammatory cytokine levels.
  • While FAS siRNA uptake was confirmed after HOPE, no significant differences in apoptosis or necrosis were observed compared to controls.

Conclusions:

  • FAS inhibition via siRNA therapy shows potential in decreasing IRI severity under SCS conditions in LT.
  • Integrating siRNA therapy with HOPE liver perfusion presents significant challenges.
  • Further research with optimized siRNA compounds and dosages is necessary to establish efficacy in liver HOPE perfusion.