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Related Concept Videos

siRNA - Small Interfering RNAs02:30

siRNA - Small Interfering RNAs

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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...
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Experimental RNAi02:15

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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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RNA Interference01:23

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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.
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Related Experiment Video

Updated: Sep 15, 2025

Chitosan/Interfering RNA Nanoparticle Mediated Gene Silencing in Disease Vector Mosquito Larvae
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Protection from malaria infection using liver-targeted siRNA.

R W J Steel1, A Schepis1, T Nguyen2

  • 1Center for Global Infectious Disease Research, Seattle Children's Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA.

Molecular Therapy. Methods & Clinical Development
|July 18, 2025
PubMed
Summary
This summary is machine-generated.

Small interfering RNA (siRNA) targeting CD81 blocked malaria parasite liver infection in mice and humanized mice, preventing disease onset. This host-directed RNA interference approach shows promise for malaria prevention.

Keywords:
Plasmodiumliver infectionmalariamalaria preventionsiRNA

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Area of Science:

  • Hepatology
  • Immunology
  • Infectious Diseases

Background:

  • Malaria parasites infect the liver asymptomatically before causing disease.
  • CD81 on hepatocytes is a key entry receptor for Plasmodium falciparum sporozoites.
  • Exploiting CD81 for malaria prevention remains a challenge.

Purpose of the Study:

  • To investigate the efficacy of CD81-targeted small interfering RNA (siRNA) for malaria prevention.
  • To assess the ability of siRNA to silence CD81 expression in hepatocytes in vivo.
  • To evaluate the impact of CD81 silencing on Plasmodium infection in a mouse model.

Main Methods:

  • N-acetylgalactosamine (GalNAc)-conjugated siRNA targeting CD81 was administered to mice.
  • CD81 expression in the liver was measured following siRNA administration.
  • Mice were infected with malaria sporozoites to assess liver and blood stage infection.
  • Human liver-chimeric mice were used to evaluate efficacy against human Plasmodium falciparum.

Main Results:

  • CD81-targeted GalNAc-siRNA efficiently silenced CD81 expression in mouse and human hepatocytes in vivo.
  • siRNA treatment blocked malaria parasite liver infection in a dose-dependent manner.
  • Preventing liver infection with siRNA halted the onset of blood stage malaria.
  • Reduced Plasmodium falciparum infection was observed in human liver-chimeric mice.

Conclusions:

  • CD81-targeted siRNA represents a promising host-directed strategy for malaria prevention.
  • RNA interference offers a clinically relevant approach to block parasite liver stage infection.
  • This method effectively prevents malaria by targeting a critical host factor for parasite entry.