An Overview of RNAi Therapy

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RNA interference (RNAi) therapy is a type of biotechnology that targets and alters genes. It is being explored to treat a number of different conditions, including cancer. In August 2018, the FDA approved the first RNAi therapy drug, called Onpattro, for use in patients with a rare disease called hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis). hATTR is characterized by an abnormal protein buildup in organs and tissues, which may eventually result in the loss of sensation in the extremities.

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RNAi therapy is created by harnessing a process that naturally occurs in the body's cells at the genetic level. There are two main components of genes: deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Most people have heard of DNA and would recognize its classic double-stranded, or double helix, appearance, but they may not be familiar with typically single-stranded RNA.

While the importance of DNA has been known for many decades, we've only started to get a better understanding of RNA's role in recent years.

DNA and RNA work together to determine how a person's genes work. Genes are responsible for everything from determining a person's eye color to contributing to their lifetime risk of certain diseases. In some cases, genes are pathogenic, meaning they can cause people to be born with a condition or develop one later in life. The genetic information is found in DNA.

In addition to being a "messenger" for genetic information housed in DNA, RNA can also control how — or even if — certain information is sent. Smaller RNA, called micro-RNA or miRNA, has control over a lot of what happens in the cells. Another type of RNA, called messenger RNA or mRNA, can turn off a signal for a certain gene. This is referred to as "silencing" the expression of that gene.

In addition to messenger RNA, researchers have found other types of RNA, too. Some types can turn on or "ramp up" the directions for creating certain proteins or change how and when the instructions are sent.

When a gene is silenced or turned off by RNA, it's referred to as interference. Therefore, researchers developing biotechnology that harnesses the naturally occurring cellular process named it RNA interference, or RNAi, therapy.

RNAi therapy is still relatively new biotechnology. Less than a decade after publishing a paper on the method's use in worms, the team of scientists credited with creating the technology won the 2006 Nobel Prize in Medicine.

In the years since researchers around the world have been exploring the potential for using RNAi in humans. The goal is to develop therapies that can be used to target certain genes that cause or contribute to health conditions. While there are already gene therapies that can be used this way, harnessing the role of RNA opens up the potential for more specific treatment.

How It Works

While DNA is famously double-stranded, RNA is almost always single-stranded. When RNA has two strands, it's almost always a virus. When the body detects a virus, the immune system will try to destroy it.

Researchers are exploring what happens when another type of RNA, known as small-interfering RNA (siRNA), is inserted into cells. In theory, the method would provide a direct and effective way to control genes. In practice, it's proved to be more complicated. One of the foremost problems researchers have encountered is getting altered, two-stranded RNA into the cells. The body thinks double-stranded RNA is a virus, therefore it launches an attack.

Not only does the immune response prevent the RNA from doing its job, but it can also cause unwanted side effects.

Potential Benefits

Researchers are still discovering potential uses for RNAi therapy. Most of its applications are focused on treating diseases, particularly those that are rare or difficult to treat, like cancer.

Scientists are also able to use the technique to learn more about how cells work and develop a deeper understanding of human genetics. Researchers can even use RNAi splicing techniques to study plants and experiment with engineered crops for food. Another area scientists are especially hopeful for is vaccine development, as RNAi therapy would provide the ability to work with specific pathogens, such as a certain strain of a virus.


RNAi therapy holds promise for a number of uses, but it also poses significant challenges. For example, while the therapy can be specifically targeted to only affect certain genes, if the treatment "misses the mark" a toxic immune response could result.

Another limitation is that RNAi therapy is good for turning off genes that cause problems, but that's not the only reason someone might have a genetic condition. In some cases, the problem is that a gene is not turned off when it should be or is underactive. RNA itself can turn genes on and off. Once that ability is harnessed by researchers, the possibilities for RNAi therapy will expand.


In 2018, the FDA approved a drug called patisiran to be sold under the brand name Onpattro. Using small interfering ribonucleic acid therapy (siRNA), Onpattro is the first of the new class of drugs to be approved by the FDA. It's also the first approved treatment for patients with a rare genetic condition called hereditary transthyretin-mediated amyloidosis (hATTR).

It's believed that about 50,000 people worldwide have hATTR. The condition affects several parts of the body, including the gastrointestinal system, the cardiovascular system, and the nervous system. Due to a genetic mutation, a protein produced by the liver called transthyretin (TTR) doesn't function correctly. People with hATTR experience symptoms due to a buildup of this protein in different parts of their bodies.

When other body systems are affected by the buildup of TTR, people with hATTR experience a range of symptoms including gastrointestinal issues such as diarrhea, constipation, and nausea, or neurologic symptoms that may appear similar to a stroke or dementia. Cardiac symptoms, such as palpitations and atrial fibrillation, can also occur.

A small number of adult patients with hATTR will be able to use Onpattro specifically to treat the nerve disease (polyneuropathy) that occurs due to a buildup of TTR in the nervous system.

The symptoms of polyneuropathy are typically felt in the arms and legs.

Onpattro is infused into the body and goes directly to the liver where it turns off production of the damaging proteins. By slowing or stopping the buildup of the proteins in the peripheral nerves, the goal is to reduce the symptoms (such as tingling or weakness) that develop as a result.

When the drug was being tested, patients who were given Onpattro noticed an improvement in their symptoms compared to those who were given a placebo (no medication). Some patients reported side effects related to receiving infusion therapy, including flushing, nausea, and headache.

As of the beginning of 2019, Alnylam, the manufacturer of Onpattro, is developing additional drugs using RNAi therapy which they hope will also receive FDA approval.

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By Abby Norman
Abby Norman is a freelance science writer and medical editor. She is also the author of "Ask Me About My Uterus: A Quest to Make Doctors Believe in Women's Pain."