The genetic technology that could slow, stop, or reverse chronic disease

When you imagine a perfect day, what sounds come to mind? Maybe it’s leaves rustling during a hike with friends, waves brushing the shore while you flip through a beach read, or the laughter of family at a weekend picnic. For millions living with chronic diseases, these experiences can feel distant. Instead, the rattle of pill bottles, the static of doctors’ office hold music, or the mechanical beeps of hospital exam rooms can persist.

Today, more than half of Americans live with at least one chronic disease_.¹ Heart disease alone accounts for one in every three deaths,² while Alzheimer’s disease is a top 10 leading cause of death.³ Modern medicine has helped people manage symptoms, but what if science could go deeper?

That’s now happening. Researchers have uncovered genes that play a role in a number of chronic conditions. And they have invented new types of therapies to target their genetic roots. One of the most promising developments is a therapeutic approach called RNA interference, or RNAi. It’s a form of gene silencing.

The backstory

RNAi was discovered in the late 1990s, when scientists made a remarkable finding: double stranded RNA could silence genes.⁴ This provided deeper understanding into how genes are regulated naturally within cells.

This realization was so groundbreaking it earned the 2006 Nobel Prize.⁵

Other scientists recognized the potential to use RNAi to treat disease, but turning that idea into medicines was far from simple. Researchers faced daunting challenges as they figured out how to deliver the RNAi therapeutics they created to cells. Scientists at a biopharmaceutical company called Alnylam persevered and pioneered the first RNAi therapeutic, which was approved by the FDA in 2018 to treat a rare genetic disorder.⁶

Today there are seven FDA-approved RNAi therapeutics, six of them discovered by Alnylam. With the underlying RNAi therapeutic technology now proven, progress is accelerating. There are approximately 150 RNAi therapeutic programs in clinical development across the industry, including for common conditions like cardiovascular disease and Alzheimer’s.

“When I was a medical student and resident, I cared for many patients with chronic diseases and in most instances, there wasn’t much we could do to help them beyond managing their symptoms,” said Pushkal Garg, Alnylam’s chief research and development officer. “It’s a new era in medicine. RNAi therapeutics, combined with a deeper understanding of the genetic underpinnings of disease, have the potential to change the course of many chronic diseases and help millions of patients.”

How gene silencing works

So, how does RNAi actually work?

Think of your body as a giant orchestra. DNA is the sheet music. Proteins are the musicians. When they are in sync, you get harmony, health. But sometimes the sheet music contains a mistake and the violinists play the wrong note, or the trumpets play too loud… The whole performance suffers, and disease can take the stage.

RNAi acts like the orchestra conductor. With incredible precision and in real-time, it identifies the problem and quiets the disruptive protein, instead of rewriting the score. And because it doesn’t alter DNA, it comes with a built-in safety feature: unlike other genetic medicines that make permanent changes, this approach can be adjusted over time.

In molecular terms: scientists design a short double-stranded RNA that genetically matches part of a messenger RNA, the instructions for making a protein. Once inside the cell, the double-stranded RNA, with some help from other protein partners, hunts down the matching mRNA. When it finds it, it slices it apart, causing it to degrade and thereby erasing the instructions it carries before the problematic protein can be made.

RNAi therapeutics work upstream of standard medicines, treating disease at its source. This approach, combined with the fact that RNAi works continually for long periods of time, means that effects of a single dose can last for months. For patients, this could mean slowing disease. Stopping it. Maybe even reversing it. All without the burden of taking a daily pill.

Tens of thousands of patients have already benefited from RNAi therapeutics. Now Alnylam is continuing to develop more therapies across both rare and common conditions like high blood pressure and neurodegenerative diseases.⁷

“RNAi is opening doors in medicine, giving us the ability to strike difficult diseases at their source instead of just managing symptoms,” said Garg. “We’re just at the start of what’s possible, and I’m hopeful that scientists will continue to deliver life-changing therapies that help patients return to living life to the fullest.”