# How Modified RNA Tricks Cells Into Making Proteins Without Triggering Attacks

> A breakthrough method for using modified RNA to deliver instructions to cells without causing the body to reject the treatment as a foreign invader.

- **Patent:** US 8278036
- **Original title:** RNA containing modified nucleosides and methods of use thereof
- **Owner:** University of Pennsylvania Penn
- **Granted:** 2012
- **Status:** Public domain (expired)
- **Times cited:** 322
- **Field:** biotech, pharmaceutical

## What it does

This patent describes a way to make synthetic RNA molecules that look and act like natural RNA so the body's immune system doesn't attack them. By replacing the standard building block uridine with a modified version called pseudouridine, the RNA avoids triggering the cell's internal alarm systems, such as Toll-like receptors. This allows the cell to read the RNA instructions and produce a specific protein, like erythropoietin, without the cell shutting down or releasing inflammatory cytokines. The method includes synthesizing this RNA in a lab and delivering it to cells, often inside protective lipid nanoparticles.

## What it does NOT cover

- Does not cover naturally occurring RNA found in the body.
- Does not cover unmodified RNA that triggers a standard immune response.
- Does not cover DNA-based gene therapy or viral vector delivery systems that do not use the specified modified RNA.
- Does not claim the specific protein being encoded, only the method of using modified RNA to induce its production.

## The clever bit

The inventors realized that the immune system's hostility toward synthetic RNA wasn't a bug, but a feature—it was detecting the lack of specific chemical modifications found in natural RNA. By simply swapping one building block, they turned a 'foreign' signal into a 'self' signal.

## Real-world examples

1. Pfizer-BioNTech COVID-19 vaccine
2. Moderna COVID-19 vaccine
3. Experimental mRNA cancer vaccines

## Why it matters

This technology is the foundation for modern mRNA vaccines, including those used against COVID-19. Before this discovery by Katalin Kariko and Drew Weissman, synthetic RNA was largely ignored by the medical community because it was too inflammatory to be useful as a therapy. It effectively unlocked the potential of RNA as a programmable medicine.

## Frequently asked questions

### What does How Modified RNA Tricks Cells Into Making Proteins Without Triggering Attacks cover?

A breakthrough method for using modified RNA to deliver instructions to cells without causing the body to reject the treatment as a foreign invader.

### Who owns patent US 8278036?

University of Pennsylvania Penn owns this patent, granted in 2012.

### When does this patent expire?

This patent has expired and is now in the public domain — anyone can use the invention freely.

### What is patent US 8278036 cited by?

This patent has been cited by 322 later patents that build on its ideas.

### What problem does this patent solve?

This technology is the foundation for modern mRNA vaccines, including those used against COVID-19. Before this discovery by Katalin Kariko and Drew Weissman, synthetic RNA was largely ignored by the medical community because it was too inflammatory to be useful as a therapy. It effectively unlocked the potential of RNA as a programmable medicine.

### What does this patent NOT cover?

Does not cover naturally occurring RNA found in the body.

**Full plain-English explainer:** https://patentbrief.org/patent/us/8278036/rna-containing-modified-nucleosides-and-methods-of-use-thereof

**Original patent:** https://patents.google.com/patent/US8278036

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_Source: PatentBrief — https://patentbrief.org. Patent facts are from public records; the plain-English explanation is PatentBrief's._


## Related patents

Semantically similar inventions in the PatentBrief corpus:

- [How Moderna's mRNA Vaccine Technology Targets Betacoronaviruses](https://patentbrief.org/patent/us/10702600/betacoronavirus-mrna-vaccine) — A patent describing a specific mRNA vaccine design that uses lipid nanoparticles to deliver genetic instructions for building parts of a betacoronavirus to trigger an immune response.
- [New Nanoparticles for Delivering Large RNA Medicines to Cells](https://patentbrief.org/patent/us/12419940/compositions-and-methods-for-modified-dendrimer-nanoparticle-delivery) — This patent describes a specific type of modified dendrimer nanoparticle designed to efficiently deliver large RNA molecules, like replicating RNA, into cells for therapeutic, prophylactic, or diagnostic purposes, notably without using cholesterol.
- [How an mRNA Vaccine Teaches Your Body to Fight Rabies](https://patentbrief.org/patent/us/12083190/rabies-vaccine) — This patent describes a method for creating an immune response against the rabies virus by injecting a specific messenger RNA molecule that instructs cells to produce a key rabies protein.
- [Using Two Specific RNAs to Teach the Body to Fight Lung Cancer](https://patentbrief.org/patent/us/20220096616/composition-for-treating-lung-cancer-particularly-of-non-small-lung-cancers-nscl) — This patent describes an active composition containing two specific messenger RNAs, NY-ESO-1 and MAGE-A3, designed to stimulate an immune response in a mammal to treat lung cancer, especially non-small cell lung cancers.
- [How an mRNA Vaccine for Lung Cancer Teaches the Immune System to Fight](https://patentbrief.org/patent/us/20160168227/composition-and-vaccine-for-treating-lung-cancer) — This patent describes a specific mRNA vaccine designed to treat lung cancer by instructing the body's cells to produce six distinct tumor proteins, thereby training the immune system to recognize and attack cancer cells.
