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rna

What are RNA therapies?

A new kind of medicine that temporarily changes what proteins are made.

By East River Notes 14 min read

What RNA therapies are, and how they work

  • Every protein in a body starts as a short-lived message written in RNA.
  • RNA therapy acts on that message to alter the protein-making process.
  • An mRNA vaccine trains the immune system to recognize future threats.
  • An RNA therapy is different – it either silences or redirects existing mRNA in the body. It does not introduce new mRNA, it does not have the body make foreign proteins, and it is designed to not trigger an immune response.
  • RNA therapies historically addressed only rare diseases, but recently they are increasingly targeting larger populations and more common diseases.

The simple version

An RNA therapy is a short piece of genetic code that acts like a temporary off switch for a specific protein.

What is RNA, and what does it do?

Most drugs act on a finished protein – blocking it, activating it, or supplying it. RNA therapy works by changing how the protein is made, or not made, at the source.

DNA is the master copy of all the instructions for the body, and it does not leave the nucleus of a cell. When a cell needs a protein, it copies a specific part of DNA for how to make that one protein – this copy is called messenger RNA (mRNA). Ribosomes in the cell read the mRNA and build the protein. For details on the basics of genomics, see our article on sequencing.

mRNA is a set of instructions that tells a cell how to make a protein. In this article, “messages” and “instructions” are used interchangeably for mRNA to help better describe the mechanisms.

What is an mRNA vaccine?

As many learned during COVID, an mRNA vaccine works by training the immune system to recognize a specific type of virus. The body’s cells read the vaccine’s mRNA and make a protein marker – a harmless piece of the virus – then the immune system learns to attack it.

Exhibit 1How an mRNA vaccine works (illustrative)
Four numbered steps run left to right: a bead-ringed fat droplet holding a blue mRNA strand; a cell taking the droplet in and releasing the strand; a cell turning the strand into three-lobed protein markers; and a spiky immune cell surrounded by antibodies, one holding a marker. 1 2 3 4 Fat dropletcarries the mRNAA tiny fat dropletprotects the mRNAuntil it reaches cells. Cells take upthe messageCells near theinjection site absorbthe mRNA and releaseit inside. Cells makethe protein markerThe mRNA is a temporaryset of instructions thatcells use to make aharmless protein marker. Immune systemlearns the markerThe immune systemrecognizes the markerand builds a lastingresponse for the future.
Source: East River Notes, from company presentations, filings, and other publicly available information. Schematic. As of November 2026.

Fever and aches after vaccination reflect the immune system’s early inflammatory response. Cells have built-in sensors that can recognize unfamiliar RNA, and the fat-based particles carrying the mRNA can also stimulate the immune system. Together, these processes help create the conditions for the body to build lasting immunity.

The same idea is now being tested against cancers: the tumor’s mutations are sequenced and an mRNA is written to match them, so the immune system learns to recognize the cancer cells.

RNA therapies – not to be confused – are different.

What is an RNA therapy?

RNA therapies turn off or change how proteins are made – but do not make proteins.

RNA therapies act on mRNA – the messages the body already produces. The drug products are called oligonucleotides – short strands of ~20 genetic letters (vs. ~4,000 for an mRNA vaccine).

An oligonucleotide acts like a search term: its sequence of letters allows it to find and stick to a particular stretch of the mRNA.

Once the oligonucleotide finds its target, it can do one of two things: silence the message or redirect how it is read.

Framework – Silence or redirect

Silence. If a disease is caused by a particular protein, the goal is to make less of it. An siRNA drug finds and destroys specific mRNA instructions for that protein. This process is called RNA interference. Without the message, the cell produces less of that protein.

Redirect. Sometimes the problem is not that a protein is harmful, but that the body is not making the correct version of it. Certain ASOs can bind to a message while it is being prepared, changing which sections are included in the final instructions. This process, called splice switching, can help the cell produce a different or more functional version of the protein.

The distinction is simple: silencing reduces the production of a protein; redirecting changes which version of the protein gets made. Neither requires changing the underlying DNA.

This article focuses on two established types – small interfering RNA (siRNA) and antisense oligonucleotides (ASOs).

Exhibit 2Silence or redirect: what RNA therapies do to a message
Three rows. In the siRNA row and the first antisense row the message is broken where the drug binds, and only one of three proteins gets made; in the redirect row a section of the message loops out and the protein is made with one part changed, marked in blue. Drug What happens to the message Result siRNASilence guide strand in the cell’s cutting enzyme less protein ASOSilence the strand marks the message to be cut less protein ASORedirect a section is skipped the strand hides one splicing signal a different version Blue marks the drug (oligonucleotides), and the part of the protein that changes.
Source: East River Notes, from company presentations, filings, and other publicly available information. Schematic; not to scale. As of November 2026.

Unlike mRNA vaccines, siRNA and ASO medicines are not designed to teach the immune system to recognize a new protein. RNA therapies are built to avoid triggering the immune system. Their strands are heavily altered chemically, so the immune system does not notice them, and most are given without the fat droplet. And because they act on messages the body already makes rather than instructing cells to build a foreign protein, there is nothing new for the immune system to learn.

How does siRNA work?

Small interfering RNA (siRNA) consists of two short strands of RNA paired together, each about 20 letters long.

The two strands enter a cell together. One strand is the guide strand, which carries the instructions for finding the target RNA. The other is the passenger strand, which helps the guide strand enter a protein called Argonaute 2, which acts like a pair of molecular scissors.

The guide helps Argonaute 2 find a specific message to cut. Without the message, the cell can no longer use that copy to make its protein.

Exhibit 3One siRNA guide cuts many copies of a message
Three steps. A paired siRNA enters the cell; inside the enzyme Argonaute 2 one strand is kept as the guide and the other is thrown away; the same guide then cuts copy after copy of the matching message. 1siRNA entersas a pair 2One strand is keptas the guide 3The same guidecuts many messages Two short strands(~20 letters each) Argonaute 2 passenger strandis discarded repeats many times
Source: East River Notes, from company presentations, filings, and other publicly available information. Schematic; not to scale. As of November 2026.

The guide can be reused. After destroying one message, the same guide and enzyme can find and destroy another. A relatively small amount of siRNA can therefore substantially reduce production of a targeted protein. Most approved siRNA drugs are built to be taken up by the liver, and liver cells hold a store of the drug and release it slowly – which is why one injection can work for months.

Exhibit 4With siRNA, fewer messages survive and far less protein is made
Two panels. Before siRNA, nine intact messages feed nine proteins. After siRNA, seven of the same messages lie cut and fading, several beside scissors; the two left intact make the only two proteins. Before siRNA Many RNA messages are available, so the cell makes a lot of protein. RNA messages for one protein Protein made After siRNA siRNA guides find and cut many of the messages, so the cell makes much less protein. siRNA cuts many RNA messages Much less protein made
Source: East River Notes, from company presentations, filings, and other publicly available information. Schematic; not to scale. As of November 2026.

How does an antisense oligonucleotide work?

An antisense oligonucleotide (ASO) is a short, single strand of genetic material that attaches to a particular RNA message. Depending on how it is designed, it can either cause the message to be destroyed or change how the cell assembles it.

Framework – Destroy or change the instructions

Destroy. Some ASOs, called gapmers, have a short stretch of DNA letters in the middle, surrounded by chemically modified ends. When a gapmer attaches to its target, the DNA portion attracts an enzyme called RNase H1, which cuts the RNA message apart. The ASO remains intact and can move on to another copy. The result is similar to siRNA: fewer messages survive, so less of the corresponding protein is made.

Change. Other ASOs work differently. Before an RNA message is ready to make a protein, it often goes through a cut-and-join step called splicing. The cell removes certain sections of the original message and joins the remaining pieces together. A splice-switching ASO can cause the cell to skip a section it otherwise would not – or keep one it would otherwise remove. This changes the final instructions and, consequently, the protein the cell makes.

Exhibit 5An ASO either destroys the message or changes how it is assembled
Two stacked panels. In the first, an ASO binds a message, an enzyme cloud cuts it, and torn pieces scatter. In the second, an ASO binds a message, a section loops out at the splice signal, and the finished message keeps that section with the ASO but drops it without. 1Destroy the messageGapmer ASO ASO ASO binds RNase H1 Enzyme cuts Instructions destroyed 2Change how the message is assembledSplice-switching ASO ASO ASO binds splice signal Splicing changes with ASO123 without ASO13 Instructions changed
Source: East River Notes, from company presentations, filings, and other publicly available information. Schematic; not to scale. As of November 2026.

What can RNA therapies treat today?

As of November 2026, about twenty siRNA and antisense drugs are approved in the U.S., for conditions including inherited metabolic disorders, neurological diseases, blood disorders, and more recently, cardiovascular and infectious diseases.

Some medicines reduce harmful proteins. RNA therapies can treat diseases where abnormal proteins accumulate and damage organs. Others help the body produce a needed protein, or let cells make a shortened but partly working version of the missing protein.

What these diseases have in common is that one protein is the problem, and the cells that make it can be reached – most often in the liver, or by injection into the spinal fluid.

Exhibit 6Approved RNA therapies by disease area
Disease areaConditions with an approved RNA therapy
Protein-misfolding diseasesTransthyretin amyloidosis (nerves and heart)
Inherited metabolic diseasesAcute hepatic porphyria, primary hyperoxaluria
Neurological and muscle diseasesSpinal muscular atrophy, Duchenne muscular dystrophy, Alexander disease
Blood and immune disordersHemophilia, hereditary angioedema
Cardiovascular and metabolic diseasesHigh LDL cholesterol, severe hypertriglyceridemia
Infectious diseasesChronic hepatitis B
Source: East River Notes, from company presentations, filings, and other publicly available information. As of November 2026.

What’s next for RNA therapies?

For most of their history, RNA therapies focused on rare diseases affecting just hundreds or thousands of patients. Until 2021, every approved RNA therapy was for a rare disease.

That is beginning to change. RNA therapies approved in 2021 (high cholesterol) and 2026 (severe triglycerides, chronic hepatitis B) each treat a condition affecting more than a million people in the U.S.

Exhibit 7RNA drugs have moved from diseases of thousands to diseases of millions
Dots plot each approval by year against patient numbers on a log scale: gray dots for rare diseases sit low from 2016 to 2026, three blue dots rise above a million people in 2021 and 2026, and one hollow dot for a drug still in late-stage trials sits at the top right. 1001,00010,000100,0001 million10 million100 million People with the condition, approximate (log scale) 20162018202020222024202620282030 high cholesterol (2021) severe triglycerides (2026) hepatitis B (2026) hypertension (sponsor expects ~2030) transthyretin heart disease (2025) spinal muscular atrophy (2016) Duchenne (2016) transthyretin amyloidosis (2018) primary hyperoxaluria (2020) hemophilia (2025) Alexander disease (2026) approved, rare disease approved, over a million people not yet approved (in late-stage trials)
Source: East River Notes, from FDA approval records, company announcements, and other publicly available information. Population estimates are approximate and mostly for the U.S. As of November 2026.

Many of the rare-disease drugs act on proteins made in the liver, because the liver is the one organ RNA therapies reach reliably today. The liver remains the easiest organ to target with many RNA medicines, particularly those delivered through the bloodstream. Reaching other tissues is harder, although direct delivery to the spinal fluid has made several neurological treatments possible.

For diseases requiring long-term treatment, the lasting effects of some RNA medicines could provide an alternative to daily pills or more frequent injections. And unlike cell and gene therapies, these medicines do not permanently change the underlying DNA.

Takeaways

  • mRNA vaccines teach the immune system to recognize a protein; RNA therapies change how cells produce proteins.
  • siRNA silences targeted RNA messages; ASOs can either destroy messages or change how they are assembled.
  • RNA therapies target a problematic protein that the body makes at the source, without altering the underlying genes.
  • RNA therapies are moving from treating rare diseases only to treating conditions affecting millions.

One line to remember

RNA therapy treats patients by intervening in the protein-making process inside cells.

General, educational, and informational research only, not tailored to your situation. Nothing here constitutes investment, legal, medical, or other professional advice; an offer to sell or a solicitation of an offer to buy any security; promotional or marketing material; or a recommendation. The author may hold positions in the securities or sectors discussed. Do your own research and consult a licensed professional. Full disclosures at www.eastrivernotes.com/disclosures.

Notes

The mechanisms described here are synthesized from peer-reviewed literature, FDA prescribing information, company presentations, filings, and other publicly available information; approval dates and drug counts follow FDA records and company announcements as of November 2026. Quantitative figures in the text and exhibits – strand lengths, dosing intervals, and the number of people with each condition – are rounded and approximate, representative of published studies and the current market rather than values precise to any single product or patient; population figures are the number of people with a condition, mostly in the U.S., not the number treated. Exhibits are illustrative and schematic, not to scale. Some technical terms are deliberately simplified for a general reader without changing their underlying meaning. This primer favors durable concepts over point-in-time statistics.

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