RNA interference against viruses: strike and counterstrike

Joost Haasnoot1, Ellen M Westerhout, Ben Berkhout

  • 1Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam, Academic Medical Center of University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.

Nature Biotechnology
|December 11, 2007
PubMed

Insights

RNA interference (RNAi) offers a promising gene-silencing approach for treating diseases. However, challenges like toxicity, delivery, and viral escape mechanisms must be addressed for effective RNAi therapeutics.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biotechnology

Background:

  • RNA interference (RNAi) is a natural gene-silencing process triggered by double-stranded RNA.
  • RNAi therapeutics show potential for treating cancer, infectious diseases, and genetic disorders.
  • Antiviral RNAi strategies are under investigation, with some compounds in clinical trials.

Purpose of the Study:

  • To explore the therapeutic potential of RNA interference (RNAi).
  • To identify challenges and considerations for developing effective RNAi-based therapeutics.
  • To discuss strategies for overcoming obstacles in RNAi drug development.

Main Methods:

  • Review of existing literature on RNAi mechanisms and applications.
  • Analysis of challenges in RNAi therapeutic development, including toxicity and delivery.
  • Examination of viral evasion strategies against RNAi.

Main Results:

  • RNAi can induce specific inhibition of virus replication.
  • Toxicity and cellular delivery issues may hinder RNAi therapeutic development.
  • Viruses have evolved mechanisms to counteract RNAi.

Conclusions:

  • RNAi is a powerful tool with therapeutic promise.
  • Overcoming delivery, toxicity, and viral resistance is crucial for clinical success.
  • Careful design is essential for developing effective RNAi-based antiviral therapies.

Related Concept Videos

Antiviral Nucleoside Inhibitors01:22

Antiviral Nucleoside Inhibitors

Antiviral Nucleoside InhibitorsAntiviral nucleoside inhibitors are structural analogs of natural nucleosides that interfere with viral DNA or RNA synthesis. These compounds selectively target viral polymerases due to their resemblance to host nucleosides, thereby disrupting viral genome replication.Mechanism of Acyclovir ActionAcyclovir is a guanosine analog with a three-carbon acyclic side chain. It selectively targets herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2),...
The Antiviral System of Bacteria and Archaea: CRISPR01:23

The Antiviral System of Bacteria and Archaea: CRISPR

CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats is a adaptive immune system found in bacteria and archaea that protects against viral infections. This system enables prokaryotic cells to identify, remember, and neutralize foreign genetic elements, primarily bacteriophages, by storing fragments of the invader’s DNA as a genetic memory.The CRISPR immune response begins during an initial infection. Cas (CRISPR-associated) proteins play a central role in this defense.
Viral Recombination00:57

Viral Recombination

Cells are sometimes infected by more than one virus at once. When two viruses disassemble to expose their genomes for replication in the same cell, similar regions of their genomes can pair together and exchange sequences in a process called recombination. Alternatively, viruses with segmented genomes can swap segments in a process called reassortment.
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
Inhibitors Of Virion Release01:25

Inhibitors Of Virion Release

Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...
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...