An overview of RNA-targeted therapy for HAE

Hereditary angioedema (HAE) is a genetic disorder that causes recurring episodes of swelling in different areas of the body, including the skin, the gastrointestinal tract, and the throat. HAE attacks can cause significant pain and discomfort, and attacks that involve the throat or airways can be life-threatening.

There is currently no treatment that can cure HAE, though there are therapies that can help manage this condition.

Everyone with HAE should be prescribed an on-demand medication to be taken at the first symptoms of an attack. On-demand medications lessen the severity of symptoms and shorten the duration of attacks, but do not prevent attacks.

Prophylactic medications prevent attacks. Some people need to take a prophylactic medication continuously, and nearly everyone with HAE needs to take one at some point. Physical trauma or injury is one of the most common triggers for attacks, and short-term prophylactic medications become necessary when undergoing dental work or other medical procedures.

RNA-targeted therapy is a prophylactic treatment for HAE

Medical researchers are looking for new ways to treat and manage HAE, and several new therapies have become available in recent years. This includes the first RNA-targeted prophylactic treatment, which was approved by the U.S. Food & Drug Administration (FDA) in 2025. Multiple other therapies are in development, including potentially curative gene therapies.

Like other prophylactic therapies, RNA-targeted therapy helps reduce the frequency of HAE attacks. However, RNA-targeted therapy prevents HAE attacks through a different mechanism than other treatments.

What’s happening during an HAE attack?

Most cases of HAE are caused by genetic mutations that disrupt the body’s ability to produce a protein called C1 inhibitor. Either the body does not produce enough C1 inhibitor or produces C1 inhibitor that does not function normally.

C1 inhibitor acts as a control for the immune system. Its functions include regulating the amount of a substance called bradykinin.

Bradykinin is one of several substances activated by the immune system in response to an injury or infection.

Bradykinin causes blood vessel walls to become more permeable, allowing substances to pass from blood vessels into surrounding tissues. This permeability helps nutrients, immune proteins, and oxygen reach damaged or infected cells.

But when there is too much bradykinin, large quantities of fluid and other substances leak into body tissues, which leads to unwanted and sometimes severe swelling. Bradykinin also activates pain receptors found on nerves, which is why HAE attacks are often painful.

There are also rare types of HAE where C1 inhibitor is normal, but other genetic mutations create excess amounts of bradykinin.

The most commonly used prophylactic treatments for HAE work by adding more functioning C1 inhibitors into the body or by blocking an enzyme that activates bradykinin.

How does RNA-targeted therapy prevent HAE attacks?

RNA, or ribonucleic acid, is a molecule found inside cells that carries out many functions, including making proteins. There are several different types.

The RNA-targeted therapy available to treat HAE is a type of drug called an antisense oligonucleotide (ASO). It binds to a type of RNA called messenger RNA, which contains instructions for making a protein called prekallikrein (PK). The ASO causes messenger RNA to degrade, so less PK is made.

Bradykinin is released as the result of a chain reaction, where one protein activates another protein activates another. PK is one of the proteins activated early in this chain. By reducing the amount of PK that is available, there will be less bradykinin and fewer HAE attacks.

In clinical trials, prophylactic therapy with ASO has been found to be an effective method of reducing HAE attacks, which has led to the approval of the first ASO/RNA-targeted prophylactic therapy for HAE.

How is RNA-targeted therapy given?

The ASO that became available in 2025 is administered as an injection given every four weeks or every eight weeks. Injections take roughly 10 seconds and can be self-administered after training from a healthcare provider.

This highlights an area of HAE treatment development that medical researchers are actively interested in—effective long-term treatments that require fewer doses.

In the past, prophylactic therapy for HAE has typically required more frequent dosing, with oral medications that need to be taken daily and some therapies that require multiple infusions per week.

Another new prophylactic therapy for HAE that was approved in 2025 requires a monthly dose with self-administered injections that take roughly 15 seconds. This also highlights the goal of developing treatments that offer long-term control with fewer doses.

It’s important to remember that no treatment is right for every single person with HAE. As someone living with HAE, it helps to stay up to date on new and emerging treatment options. For questions about specific treatment options, your best source of information about treatment will be your healthcare provider.