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As you know using RNAi we are able to prevent gene expression. so why we do not use it to stop viral genes expression?

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  • $\begingroup$ Because siRNA is very hard to deliver to tissues in an animal. That said, Tekmira is working on an siRNA based ebola therapy called TKM-Ebola. I've seen the preclinical data on monkeys at a conference last May, and it looked pretty good. Will take some time before we know if it works in humans. $\endgroup$ – user137 Nov 20 '14 at 18:49
  • $\begingroup$ Question: How do you deliver ths siRNA into the body without having it degraded? Free nucleic acids outside of cells are an alarm signal for the body. $\endgroup$ – Chris Nov 20 '14 at 18:50
  • $\begingroup$ siRNA can be chemically synthesized, allowing for modifications with 2'F or phosphorothioate backbones that resist RNase activity. I've been trying to deliver mRNA, which is too large to chemically synthesize so we're still trying to figure out how to avoid degradation. $\endgroup$ – user137 Nov 20 '14 at 19:08
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Delivering siRNA in vivo is a difficult prospect, but has been overcome in research environments and several commercial in vivo solutions are on the market see examples from Life Technologies here.

The bigger problems come from potential off-target effects. siRNA tend to be double stranded and both the 'guide' and 'passenger' strand can occasionally target multiple sequences that you did not intend. Additionally, siRNA tend to activate the body's immune system in ways that would inhibit therapy or cause excess inflammation and cell death. See the detailed review here.

In short, it is a good idea, and the current research in the field is working to overcome technical challenges, but we are not there yet.

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  • $\begingroup$ The siRNAs offered by life technologies look like the siRNA itself. How are the RNAs targeted to specific tissues and passed through cellular membranes? $\endgroup$ – user137 Nov 20 '14 at 19:35
  • $\begingroup$ RNAi therapies can be targeted by nanoparticle encapsulatin. Generally, a nanoparticle containing the siRNA can be conjugated to an antibody for the (cell surface) disease marker. Antibody brings nanoparticle to the diseased cell, cell endocytoses nanoparticle, siRNA is delivered. Alternately, I have delivered RNAi therapy by local injection in in vivo models. However, the Ebola case is much simpler. Ebola infects the endothelial cells and liver. siRNA packaged in lipid nanoparticles will accumulate in the endothelium and liver cells when intravenously injected. $\endgroup$ – Chastain Nov 20 '14 at 21:35

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