Neil’s Note: The very first newsletter article I ever wrote for HudsonAlpha described the potential impact of a technology known as RNA interference. That was more than a decade ago and the researchers who discovered RNA interference had just won the Nobel Prize. Now, we’re seeing their discovery mature into life-changing treatments. It’s incredible to imagine what the next decade of research can accomplish.
The Food and Drug Administration (FDA) approved a groundbreaking genetic treatment in August 2018. The administration gave the okay to an RNA interference (RNAi) treatment for the first time. Brian Roberts, senior scientist in the Rick Myers lab at HudsonAlpha, says that could pave the way for other similar genetic treatments.
So what is RNAi? And what makes RNAi so different from other drugs?
Most medicines target proteins, trying to stop them from functioning in whatever way is causing problems for the patient. RNAi attempts to create a new world where those proteins never get made at all.
DNA creates RNA, which in turn codes for proteins. RNAi, as the name suggests, interferes with that process by destroying the messenger RNA molecules, preventing the proteins from getting built in the first place.
The newly approved drug, Onpattro, treats peripheral nerve disease caused by hereditary transthyretin-mediated amyloidosis (hATTR). The condition causes problems in the body by creating a buildup of abnormal protein in the nerves, heart and other organs. The genetic disease is rare, affecting 50,000 people worldwide. Patients suffer immensely. Symptoms are debilitating, and the condition is often fatal.
With Onpattro, scientists have wrapped up the RNAi molecules in a lipid nanoparticle, which takes the drug directly to the liver. Then the RNAi blocks the production of the abnormal protein, slowing the progression of the disease and making the condition much more manageable.
Roberts spent years researching RNAi. He says the approval of the first RNAi based treatment will definitely cause researchers to sit up and take notice. “It’s a big moment to get that final approval,” he adds.
What’s more, Onpattro could open the door for even more RNAi treatments. Roberts says, “They’ll be right behind this one.”
RNAi was first discovered twenty years ago, and its therapeutic potential was identified almost immediately. Roberts explains, “If you could target delivery to any organ system, in theory, you could turn off any gene that is harmful. That could affect a wide variety of diseases.”
Of course, obstacles remain. For example, right now, scientists have only been able to consistently deliver RNAi molecules to the liver, using those lipid nanoparticles. A new delivery mechanism will be needed to get the molecules to other organs. But Roberts does say, “I think somebody will figure it out eventually.”
The high cost of RNAi-based treatment is an additional challenge to overcome. Onpattro is estimated to cost $450,000 per patient, per year.
RNAi treatments will have to compete for attention with CRISPR-based genetic solutions, which have become darlings of the scientific community.
CRISPR solutions go back a step further than RNAi in the genetic process. Instead of blocking messenger RNA from creating harmful proteins, CRISPR targets DNA to prevent it from making the messenger RNA in the first place.
However, it’s important to note that there are no approved CRISPR treatments yet, and the technique has its own weaknesses. For example, CRISPR would create permanent changes in DNA. If the treatment produced adverse side-effects, they could be permanent. RNAi, by contrast, would need to be reintroduced on a regular schedule, but that allows for more careful monitoring and adjustment over the course of treatment.
In the same way lipid nanoparticles encapsulate RNAi, the FDA’s approval of this new treatment encapsulates the state of treatments based on genetic alteration. While they primarily target rare cases right now, they show immense promise for medicine on the whole.
To schedule a media interview with Dr. Neil Lamb or to invite him to speak at an event or conference, please contact Margetta Thomas by email at mthomas@hudsonalpha.org or by phone: Office (256) 327-0425 | Cell (256) 937-8210
