Home » 2013 - 14 Academic Year » A New, Future Cure: RNAi

A New, Future Cure: RNAi

by Lizzy MacDougall, VI Form

St. Mark’s is in its second year of running the STEM fellowship, a class that allows eleven students the ability to pursue a research project in an area that interests them. The projects range from irrigation systems to plant growth hormones to biological studies. This last area of study is what I am researching for the year. My classmate, Hughie Auchincloss, and I are spending the year experimenting on the possibilities of using RNA interference as a cure to many kinds of diseases, such as cancer, in people who are nutrient deficient. Hopefully, our work will be the first step in helping our sister school in Haiti, St. Marguerite’s, have access to effective and affordable medicine.

In 1990, Richard A. Jorgensen stumbled upon a mechanism for silencing genes that is now called RNA interference. He was trying to make a petunia flower that was more vibrantly purple than the wild species. To do so, he inserted another copy of the purple pigment gene into the petunias hoping that this would cause the flowers to make twice as much purple pigment. Instead of growing the deep purple flowers he expected, Jorgensen grew completely white petunias.1 He concluded that some mechanism was turning off the purple gene as a reaction to the presences of duplicate genes. Years later, researchers Fire and Mello identified this mechanism and called it RNA interference (RNAi).2 They discovered that RNAi is an effective mechanism for silencing almost any gene in an organism.2 Since then, RNA interference has been studied in many branches of science as a way to identify the roles of different genes and as a possible cure to various types of diseases and viruses.

Fire and Mello determined that RNA interference can be triggered by inserting double stranded RNA (dsRNA) into an organism.2 Once the dsRNA is inside a cell, an enzyme called the Dicer cuts the dsRNA into smaller pieces named small interfering RNA (siRNA).3 The siRNA then binds to the RNA induced silencing complex (RISC) and acts as a template from which the RISC can identify corresponding messenger RNA (mRNA).3 Once the mRNA has been identified, the RISC destroys it by cleaving it into small fragments, thus effectively preventing it from being translated into complete proteins.3 This gene silencing technique has allowed researchers to identify the purposes of many genes by studying the effects when that gene is silenced.3 RNA interference has helped researchers greatly; however, millions of years before scientists discovered it, RNAi was playing a vital role in protecting organisms from infection.

Scientists believe that RNA interference’s biological role is to prevent a cell from contracting a viral infection.4 RNAi can be triggered not only by dsRNA injected into the cell, but also by microRNA, small fragments of RNA, that is made inside the cell.3 It is estimated that most organisms have hundreds of microRNA genes. These genes make microRNAs, which are never translated into an amino acid sequence. The sole purpose of the microRNAs is to help the cell identify and destroy viral RNA.3

Scientists are researching ways to use the RNAi silencing pathway to silence genes essential for the survival of a pathogen or virus, but not essential for the survival of the host organism. There has been some success with treating HIV, cancer, Huntington’s Disease, and Hepatitis C in human cultures; however, the cures have only been temporary.5 Scientists have had difficulties determining how to introduce the dsRNA into the target cells. The dsRNA is too large to be absorbed; therefore, it cannot be taken as a pill. Scientists have also experimented with exposing only the siRNA to cells, but they have found that the siRNA is also too large to be absorbed.3 Despite the difficulties, scientists are optimistic about using the RNAi pathway to treat some forms of cancer, viral infections, and other pathogenic diseases.

The FDA approved the first RNAi therapeutic trials in 2004; however, RNAi is still a long way away from being a common drug used by the public.6 Many of the drugs are still in testing stages one or two, and the safety and dosages of the drugs have yet to be determined. 7 Recently, many pharmaceutical companies have invested in firms studying RNAi. For example, in 2006 Sirna Therapeutics was bought for 1.1 billion dollars by Merck & Co.7 Even though RNAi is not yet completely ready for human use, the push for its use as a medicine has been incredibly fast, practically going from initial discover to drug trials in a period of ten years.7 Within the next ten years, RNAi will may give rise to a whole new class of drugs that cure the human body by using the body’s own mechanisms against diseases.

Lizzy MacDougall is a VI Former from a farm in Ligonier, Pennsylvania, and she lives in Thayer House. During the school year, she plays soccer, ice hockey, and lacrosse. She also enjoys hiking and competitive sailing in the summertime and on vacations. This year she is in the STEM fellowship class.


[1] Sen, G., Blau, H. (2006). A brief history of RNAi: the silence of the genes. The FASEB Journal 20, pg. 1293-1299. Retrieved Oct, 2013 from http://www.stanford.edu/group/blau/pdfs/Sen-2006-A%20brief%20history%20of%20R.pdf

2 Fire, A., Mello, C. (Feb, 1998). Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391, pg. 806-811. Retrieved Aug, 2013 from http://www.nature.com/nature/journal/v391/n6669/full/391806a0.html

3 Ullu, E., Djikeng, A., Shi, H., & Tschudi, C. (Jan. 29, 2002). RNA Interference: Advances and Questions. Philosophical Transactions: Biological Sciences, 375(1417), pg. 65-70. Retrieved September, 2013, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1692925/pdf/11839183.pdf

4 (Nov., 2012) RNA Interference Fact Sheet. National Institute of General Medical Sciences, Retreived Oct, 2013 from http://www.nigms.nih.gov/News/Extras/RNAi/factsheet.htm

5 Lewis, S. (July, 2005). The RNAi Cure? NOVA scienceNOW. Retrieved Oct, 2013 from http://www.pbs.org/wgbh/nova/body/rnai-cure.html

6 Heidersbach, A., Maia, A., et al. (Feb., 2006). RNA interference in embryonic stem cells and the prospects for future thearapies. Gene Therapy, 13 pg. 478-486. Retrieved Oct., 2013 from http://www.nature.com/gt/journal/v13/n6/full/3302723a.html

7 Perkel, J. Life Science Technologies Therapeutic RNAi: Delivering the Future? Science. Retrieved Sept. 2013 from http://www.sciencemag.org/site/products/lst_20071102.xhtml

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