APPLICATIONS OF RNAI AND RNAI-ENABLED TECHNOLOGIES
RESEARCH
A key application of RNAi is in research, where it has the possibility to elucidate much about the inner workings of the cell. The ability to suppress expression of a gene after a subject has reached maturity is a boon to research in larger organisms, as well, since the researcher no longer has to worry about fetal mortality caused by gene knockout.
In addition, the RNAi pathway allows for investigation of the complex cell-signaling apparatus, by allowing the researcher to turn on or turn off production of signaling molecules at will. Subtle application of RNAi effects allows the researcher to modulate signaling, allowing for more complex signaling experiments than simply on or off.
In addition, the researcher may utilize a library of siRNA or shRNA to screen for genes that affect a particular response. An excellent example of that type of study can be found here, where an siRNA library was used to determine genes that affected sensitivity to a TNF-related protein that can induce apoptosis in cancer cells.
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THERAPEUTICS
The use of siRNA and shRNA to mitigate disease states caused by overproduction of protein, misproduction of protein, or other diseases related to gene-expression is a new frontier in drug development. Clinical studies have been started for diseases including macular degeneration (in cases where VEGF is overproduced, leading to increased vascularization), Huntington’s Disease (where a genetic mutation causes a malformed protein to be produced, leading to nerve degeneration) and viral diseases such as HIV and RSV.
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DELIVERY PROBLEMS AND SOLUTIONS
Nucleic-acid-based products, including siRNA and the gene constructs to manufacture shRNA, are notoriously difficult-to-deliver, often getting excreted prior to effectiveness. They are vulnerable to nucleases in both the blood and the gastrointestinal system. Solutions to this problem are a fertile area of investigation, and include liposomal formulations, polymeric nanoparticles, and viral vectors.
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