RNA Interference and the Treatment of Rare Disease

On November 19, 2020, Research!America hosted an informational webinar titled “From Nobel Winning Science to Next Generation Treatment: Tracing the Path of a Rare Disease Breakthrough using RNAi.” This webinar focused on the history of RNA interference, a scientific approach that has allowed for the more effective treatment of rare disease. In the webinar, a group of panelists discussed the history of RNAi, its use in medicine today, and what the future may hold. 

Dr. Phil Sharp, professor at MIT’s Koch Institute for Integrative Cancer Research, talked about how the mechanism of RNAi was first discovered. In 1998, experiments using worms revealed that fragments of RNA could naturally trigger an effect called gene silencing. The initial basis of these findings were earlier studies of RNA splicing; in 1977, scientists first realized that RNA could be divided into exons (which produce proteins) and introns (which do not). In addition, a natural form of gene silencing called cosuppression was found in petunias.

The 21st century saw a flurry of new developments. In 2001, scientists first successfully suppressed genes using synthetic siRNA. The next year, RNAi was used to inhibit viruses such as HIV. By 2008, it was clear that RNAi was capable of being used to treat disease in humans. A decade later, the US Food and Drug Administration (FDA) approved the first ever RNAi therapy as a treatment for polyneuropathy associated with hereditary transthyretin amyloidosis (hATTR)

Dr. Akshay Vaishnaw is the president of research & development of Alnylam Pharmaceuticals, which developed ONPATTRO, the first ever RNAi therapy. Since then, the company also has another RNAi therapy approved called GIVLAARI, which is used to treat the rare disease acute hepatic porphyria. He discussed some of the challenges that had to be overcome in order to create an effective RNAi medicine. These included the difficulty of getting cells to identify the RNA, the risk of triggering inflammation, and the fact that the molecule that mediates RNAi can degenerate easily.

Alnylam is not the only company that has been developing RNAi therapies. Dr. Brian Zambrowicz, Senior VP of Functional Genomics and Chief of VelociGene® Operations at Regeneron, discussed advancements that the company has made in developing treatments that focus on the eyes and central nervous system. They have found that RNAi in the liver and CNS can halt disease progression for six months with a single dose.

RNAi has the potential to be useful in a wide variety of applications, such as pain relief, cancer treatment, infectious disease treatment, and beyond. In the future, RNAi has the potential to play a breakthrough role in new therapies.

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