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    How lipid nanoparticles deliver RNA

    Lipid nanoparticles (LNPs) are tiny fat-based particles that protect RNA and carry it into cells; they are part of the approved mRNA COVID-19 vaccines.[1] Their four lipid components and their tendency to collect in the liver shape what RNA medicines can and cannot yet do.[2][3]

    Editor reviewedStrict sourcingUpdated mRNA and next-gen vaccinesHealth and medicineLife sciences

    Why RNA needs a carrier

    A lipid nanoparticle is a tiny particle made of fat-like molecules that wraps RNA and helps it get inside cells and out into the cell’s interior, where it can be used.[2][4] The mRNA COVID-19 vaccines from Pfizer-BioNTech and Moderna both use them.[1] Without a carrier, mRNA is broken down quickly outside cells and barely gets in.[5]

    Both licensed first-generation COVID-19 mRNA vaccines, BNT162b2 and mRNA-1273, are LNP formulations.[1] Lipid formulations also carry siRNA. Onpattro, the first approved RNAi therapeutic, is a lipid formulation given intravenously every three weeks.[6][7]

    The four ingredients

    Most lipid nanoparticles mix four kinds of fat-like molecules. A special “ionizable” lipid grabs the RNA. A helper lipid and cholesterol give the particle its structure. A lipid with a PEG coating keeps particles from clumping together.[2]

    Standard LNPs combine an ionizable cationic lipid, a PEG-lipid, cholesterol and a phospholipid.[2] The ionizable lipid becomes cationic in acidic compartments, and that pH switch is central to payload release.[4] Each component has a job. The ionizable lipid complexes the mRNA, the helper lipid improves stability and delivery, and cholesterol adds structural stability. Surface PEG reduces immune recognition and lengthens circulation.[8]

    Escaping the endosome

    Cells swallow the particles into small sacs called endosomes, which become acidic. The acid flips a switch in the ionizable lipid. The lipid becomes positively charged and disturbs the sac’s wall, so the RNA can leak out into the cell, where it can be read.[4]

    In the acidic endosome, protonated ionizable lipids pair with anionic endosomal phospholipids to form cone-shaped ion pairs. These adopt an inverted hexagonal (HII) phase that destabilises the membrane and releases the cargo into the cytosol.[4]

    After the injection

    mRNA vaccines in lipid nanoparticles are mostly injected into muscle. Innate immune cells gather at the injection site and take up the particles. Once the mRNA is released inside cells, it is translated into the target antigen.[9] The antigen then trains the adaptive immune response, as described in how mRNA vaccines work.[10]

    The liver problem

    Lipid nanoparticles in the bloodstream pick up apolipoprotein E and come to resemble the body’s own fat-carrying particles. As a result they accumulate mainly in liver cells, and delivery to other organs is limited.[3] This works well when the liver is the target, as with transthyretin silencing by Onpattro.[6] For many siRNA and antisense drugs, a sugar called GalNAc now does the job without a nanoparticle by binding a receptor on liver cells.[11] See how RNA silencing drugs work. Gene-editing therapies use the same liver preference. Lipid nanoparticles can carry Cas9 mRNA and guide RNA, though reaching tissues other than the liver remains hard.[12] See lipid-nanoparticle-delivery and how gene therapy delivery works.

    Two delivery routes compared

    For mRNA vaccines and the first RNAi drug, the nanoparticle is essential. It carries the RNA in and releases it from the endosome.[1][6] For short oligonucleotides aimed at the liver, GalNAc conjugation offers a simpler alternative given by subcutaneous injection. Amvuttra, for example, is dosed quarterly.[11][13]

    Storage and access

    A 2023 review notes that mRNA vaccines need frozen or ultra-cold storage, about -20 to -80 °C. The same review calls this a logistical hurdle for low-resource settings.[14] The preparedness funder CEPI works with the WHO mRNA vaccine technology transfer programme and a regional manufacturing collaborative.[15]

    This page describes the technology. It is not medical advice.

    Questions readers ask

    What are lipid nanoparticles made of?

    They usually contain four components, an ionizable lipid, a PEG-linked lipid, cholesterol and a phospholipid.[2]

    Why do many RNA medicines target the liver?

    Lipid nanoparticles in the blood adsorb apolipoprotein E and accumulate preferentially in the liver, which limits delivery to other organs.[3]

    Was the first RNAi drug delivered with a lipid particle?

    Yes. Onpattro, approved in 2018 as the first RNAi therapeutic, is a lipid formulation given by intravenous infusion every three weeks.[6][7]

    Sources

    Each numbered claim is a statement we checked against the sources listed with it. Status shows how well established it is.

    1. [1]

      The first authorized mRNA COVID-19 vaccines, Pfizer-BioNTech's BNT162b2 and Moderna's mRNA-1273, both encode the SARS-CoV-2 spike protein and are formulated in lipid nanoparticles. confirmedas of 2023-03-01

    2. [2]

      Lipid nanoparticles used for mRNA delivery usually contain four components, an ionizable lipid, a PEG-linked lipid, cholesterol and a phospholipid (helper lipid). confirmedas of 2023-03-01

    3. [3]

      Lipid nanoparticles in the blood adsorb apolipoprotein E and therefore accumulate preferentially in the liver, which limits delivery to other organs. confirmedas of 2023-03-01

    4. [4]

      Inside the acidic endosome, ionizable lipids become positively charged and pair with the endosome's own lipids, disrupting its membrane and releasing the RNA into the cytoplasm. confirmedas of 2023-03-01

    5. [5]

      Unprotected ("naked") mRNA is quickly degraded by enzymes outside cells and is not taken up efficiently, which is why carriers are needed. confirmedas of 2018-01-12

    6. [6]

      On 10 August 2018 the FDA approved Alnylam's Onpattro (patisiran), the first approved RNAi therapeutic, which silences the mRNA encoding transthyretin to treat hereditary ATTR amyloidosis polyneuropathy. confirmedas of 2018-08-10

    7. [7]

      Onpattro is a lipid formulation given by intravenous infusion once every three weeks. confirmedas of 2018-08-10

    8. [8]

      In a lipid nanoparticle the ionizable lipid complexes the mRNA, the helper lipid improves stability and delivery, cholesterol adds structural stability, and the PEG coating reduces immune recognition and improves circulation. confirmedas of 2023-03-01

    9. [9]

      LNP-formulated mRNA vaccines are given mostly by intramuscular injection; at the injection site, innate immune cells are recruited and take up the particles, and the released mRNA is translated into the target antigen. confirmedas of 2023-03-01

    10. [10]

      Two major types of RNA are studied as vaccines, non-replicating mRNA and virally derived self-amplifying RNA. confirmedas of 2018-01-12

    11. [11]

      GalNAc is a sugar attached to oligonucleotides that binds the asialoglycoprotein receptor on liver cells and drives efficient uptake into hepatocytes. confirmedas of 2026-02-01

    12. [12]

      Lipid nanoparticles can carry Cas9 mRNA and guide RNA into tissues, but reliably targeting tissues other than the liver remains a challenge. confirmedas of 2026-10-10

    13. [13]

      On 20 March 2025 the FDA approved Alnylam's RNAi drug Amvuttra (vutrisiran) for the cardiomyopathy of transthyretin amyloidosis (ATTR-CM), based on the phase 3 HELIOS-B trial, with quarterly subcutaneous dosing. confirmedas of 2025-03-20

    14. [14]

      A 2023 review notes that mRNA vaccines need frozen or ultra-cold storage (about -20 to -80 °C), a logistical hurdle for low-resource settings. confirmedas of 2023-03-01

    15. [15]

      CEPI works with the WHO mRNA vaccine technology transfer programme and the Regionalised Vaccine Manufacturing Collaborative. confirmedas of 2026-02-01

    Revision history (2)
    1. Page created.
    2. Added the role of each lipid, what happens after injection, and links to gene-editing delivery.

    Created Oct 10, 2026. Last reviewed by an editor on Oct 10, 2026. Next scheduled review: Jan 10, 2027.

    Cite this page

    "How lipid nanoparticles deliver RNA." ContentLora, updated Oct 10, 2026. https://contentlora.com/explain/how-lipid-nanoparticles-deliver-rna

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