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This article throws light upon the two useful applications of RNA Interference. The two useful applications are: (1) Medicine and (2) Biotechnology.
Application # 1. Medicine:
It may be possible to exploit RNA interference in therapy. Although it is difficult to introduce long dsRNA strands into mammalian cells due to the interferon response, the use of short interfering RNA mimics has been more successful.
The first applications to reach clinical trials were in the treatment of macular degeneration and respiratory syncytial virus, developed by Sirna Therapeutics and Alnylam Pharmaceuticals respectively. RNAi has also been shown effective in the reversal of induced liver failure in mouse models.
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Other proposed clinical uses centre on antiviral therapies, including the inhibition of viral gene expression in cancerous cells, knockdown of host receptors and co-receptors for HIV, the silencing of hepatitis A and hepatitis B genes, silencing of influenza gene expression, and inhibition of measles viral replication.
Potential treatments for neurodegenerative diseases have also been proposed, with particular attention being paid to the polyglutamine diseases such as Huntington’s disease. RNA interference is also often seen as a promising way to treat cancer by silencing genes differentially up-regulated in tumour cells or genes involved in cell division.
A key area of research in the use of RNAi for clinical applications is the development of a safe delivery method, which to date has involved mainly viral vector systems similar to those suggested for gene therapy. Despite the proliferation of promising cell culture studies for RNAi-based drugs, some concern has been raised regarding the safety of RNA interference, especially the potential for “off-target” effects in which a gene with a coincidentally similar sequence to the targeted gene is also repressed.
A computational genomics study estimated that the error rate of off-target interactions is about 10%. One major study of liver disease in mice led to high death rates in the experimental animals, suggested by researchers to be the result of “oversaturation” of the dsRNA pathway.
Application # 2. Biotechnology:
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RNA interference has been used for applications in biotechnology, particularly in the engineering of food plants that produce lower levels of natural plant toxins. Such techniques take advantage of the stable and heritable RNAi phenotype in plant stocks. For example, cotton seeds are rich in dietary protein but naturally contain the toxic terpenoid product gossypol, making them unsuitable for human consumption.
RNAi has been used to produce cotton stocks whose seeds contain reduced levels of delta-cadinene synthase, a key enzyme in gossypol production, without affecting the enzyme’s production in other parts of the plant, where gossypol is important in preventing damage from plant pests. Similar efforts have been directed toward the reduction of the cyanogenic natural product linamarin in cassava plants.
Although no plant products that use RNAi-based genetic engineering have yet passed the experimental stage, development efforts have successfully reduced the levels of allergens in tomato plants and decreased the precursors of likely carcinogens in tobacco plants.
Other plant traits that have been engineered in the laboratory include the production of non-narcotic natural products by the opium poppy, resistance to common plant viruses, and fortification of plants such as tomatoes with dietary antioxidants. Previous commercial products, including the Flavr Savr tomato and two cultivars of ring-spot-resistant papaya, were originally developed using antisense technology but likely exploited the RNAi pathway.
