by Erika Nakajima, '21
With the high demand for rare genetic disease treatments and the limited success of small molecule drugs, there is a pressing need for novel therapeutics. Gene silencing alleviates the symptoms of genetic diseases by preventing the translation of harmful or dysfunctional proteins. Pioneering a new means of gene silencing, Alnylam, a growing biotech company stationed in Cambridge, MA, has turned the idea of RNA interference into a reality with its newly FDA approved drug. The company’s first drug treats amyloidosis, a fatal genetic disease characterized by the buildup of amyloids (protein aggregates) throughout the body.
Alnylam Pharmaceuticals was founded in 2002 and has spent the past 15 years developing their platform to deliver siRNA capable of silencing disease-causing genes. Their recent approval of drug candidate Patisiran is momentous as the CEO of Alnylam, John Maraganore, describes Alnylam’s work with RNAi as a “source of medicines.” As the first company to approve an RNAi treatment, Alnylam has everyone’s heads in the biotech industry turning to see what it will accomplish next.
The science behind RNA interference (RNAi) is straightforward in concept, but complex in practice. RNAi approaches the treatment of diseases such as amyloidosis by cleaving the mRNA transcribed from mutated genes using small-interfering RNA (siRNA). To develop a drug capable of RNAi, a company must first design an siRNA that, in combination with RNA-induced silencing complexes, is capable of finding and selectively cleaving harmful RNA. Although RNA interference was discovered as a potential therapeutic in 1998, there has been a struggle to develop a drug capable of passing both the safety and efficacy requirements of clinical trials. While designing the siRNAs that cleave the disease causing genes is relatively simple for scientists, one of the biggest challenges is delivery methods. Synthesizing a formulation that has the ability to bring the siRNAs through the blood and to cells is a difficult task that Alnylam has spent much of its time working on.
With the development of their successful lipid formulation, designing other siRNAs to treat other rare genetic diseases will hopefully move more efficiently through the drug development process. Despite having several bumps along the way in both the business and science components of their platform, the employees of Alnylam have triumphed as the leaders of RNAi. Their newly approved drug is the start of a time in which many rare genetic diseases that are otherwise neglected by other pharmaceutical companies will now have novel treatment options.
1. Morrison C. Alnylam prepares to land first RNAi drug approval.