Structural Biochemistry/RNA-Based Drugs
RNA Based Drugs
RNAi drugs are a relatively new class of drugs that rely on a mechanism known as RNA interference to inhibit or silence gene expression of certain genes . Specifically, RNAi drugs are made of synthesized small interfering RNA molecules (siRNAs) that recruit and inhibit expression of specific mRNA transcripts that code for a particular gene . Thus, the strategy behind RNAi drugs towards the treatment of cancer is that by synthesizing siRNA molecules that bind to specific mRNAs responsible for cancer-causing genes, the siRNAs, by the mechanism of RNA interference, can inactivate that mRNA transcript coding for a harmful protein and thus inhibit the translation of that protein that contributes to the symptoms of cancer and disease. Because of the ability of siRNAs to degrade mRNAs and silence their genes, RNAi based drugs are being seen as a new and innovative approach to treating cancer. Possible indications for RNA-based therapeutics include HIV, macular degeneration, and the treatment of cancerous tumor cells.
Systemic siRNA delivery
Systemic siRNA delivery strategies can be divided into passive and active (targeted) delivery.
Since the discovery of RNA interference in 2002, scientists have been actively investigating the potential of RNA interference to inhibit the expression of harmful or cancerous genes that are responsible for a variety of human diseases and cancers. For instance, scientists began to exploit RNA interference for the treatment of macular degeneration, which is a condition caused by the over-production of the VEGF gene in the eye and leads to the excess growth of blood vessels behind the retina that can eventually cause blindness.  Thus, scientists initially sought to use RNAi drugs as a way to turn off the overactive VEGF gene in the eye.
Another potential use of RNAi has been actively investigated in the treatment of HIV and is leading to the development of a novel class of HIV medications. A study published in January 2011 found that delivering an siRNA molecule bound to an RNA aptamer molecule that specifically binds to the surface of HIV cells significantly reduced expression of the HIV virus in mice injected with the virus. .
Challenges in Drug Delivery
The manufacture and marketing of RNAi drugs have been especially challenging due to difficulties in its drug delivery system; RNA is degraded in the human bloodstream, making it difficult for the drug to reach its intended site of action in human cells to be effective.  To counter this problem, scientists are investigating ways to couple RNAi molecules with other molecules to prevent the premature breakdown of RNAi molecules in the bloodstream before reaching cells or package RNAi molecules inside enclosed molecules that can transport the RNAi molecules to ensure its effective delivery. For instance, UCSF researchers are exploring ways to package siRNAs inside fat-coated molecules known as liposomes as a means of drug delivery, which are already extensively used as drug vehicles in commercial drug development.  Once transported to its intended site of action, the siRNA contents can be released out of the liposomes to silence genes at that site.
- Lewis, Susan K. “The RNAi Cure?” PBS. 1 July 2005 <http://www.pbs.org/wgbh/nova/body/rnai-cure.html>.
- Pollack, Andrew. “Drug-Makers Fever for the Power of RNA Interference Has Cooled”. The New York Times. 7 February 2011 <http://www.nytimes.com/2011/02/08/science/08rna.html?_r=1&pagewanted=all>.
- Norris, Jeffrey. “UCSF Leads Consortium to Radically Change Cancer Drug Development”. UCSF. 21 July 2009 <http://www.ucsf.edu/news/2009/07/8192/sirna-drug-development-university-labs>
- Willyard, Cassandra. “Double Whammy for HIV”. Nature. 19 January 2011 < http://www.nature.com/news/2011/110119/full/news.2011.30.html>.