Lipid Nanoparticles and Non-Viral Delivery
How lipid nanoparticles and other non-viral carriers deliver RNA and gene-editing tools, what is approved or only investigational, and where delivery still falls short.
Content last updated . This page has not been medically reviewed.
A component worth knowing: many LNPs carry a surface lipid attached to polyethylene glycol (PEG), which helps stability and also shapes immune responses, including anti-PEG antibodies. [3] Exact formulas are product-specific and not covered here.
What is investigational
Two published reports show LNPs carrying gene-editing tools, both investigational:- Gene editing for transthyretin amyloidosis (phase 1). NTLA-2001 packs messenger RNA for a gene-editing enzyme and a guide RNA into an LNP. [8] It was tested in six patients with hereditary ATTR amyloidosis with nerve damage. At day 28 the mean fall in blood transthyretin protein was 52% in the lower-dose group and 87% in the higher-dose group, with mild adverse events in that period. [8] This is a biomarker result over 28 days in six people: it does not show clinical benefit or long-term safety. See Gene Editing and CRISPR Explained.
- A one-patient base-editing therapy. After a newborn was diagnosed with severe carbamoyl-phosphate synthetase 1 deficiency, a customized LNP-delivered base-editing therapy was developed; the infant received two infusions and, in the following 7 weeks, no serious adverse events occurred, with longer follow-up needed to assess safety and efficacy. [9] One patient, no comparison group, short follow-up: insufficient evidence about how well it works. See Base Editing and Prime Editing.
Why LNPs mostly go to the liver
A 2026 review reports that the natural affinity of LNPs for the liver restricts their use elsewhere. Methods to redirect them to the lungs, spleen, brain, heart, kidney, bone and pancreas are being studied, and the review names translational bottlenecks: differences between species, immune reactions and manufacturing. [10] The abstract does not say how many of these methods have reached human trials, so treat them as early-stage research (insufficient evidence for people). Do not read this as "LNPs can treat any organ."Frequently asked questions
Are lipid nanoparticles the same as liposomes?
Not necessarily. This page covers LNPs used to carry RNA and editing tools in medicines and trials. Marketing terms such as "liposomal" in supplements are a separate topic. See the linked guide on encapsulation.
Do LNP medicines work in every organ?
No. A 2026 review says LNPs naturally favor the liver, and delivery to other organs is mostly in the research stage. [10]
Is the gene-editing LNP therapy approved?
The editing therapy described here was tested in a phase 1 study of six patients and is investigational. [8] Approved LNP-formulated medicine in this page is ONPATTRO, for its labeled use. [4]
Can the immune system react to the particle?
Yes. ONPATTRO's label lists infusion-related reactions, and antibodies to a surface PEG lipid were measured in treated patients. [4] Reviews describe anti-PEG antibody responses as a topic of ongoing study. [3]
More details: evidence, limits and cautions
The details behind this page: cautions, limits of the evidence and where sources disagree. Open any note to read it.
How to read the evidence labels
Labels used on this page: approved medicine, established, promising but limited, insufficient evidence, preclinical (cells/animals only).
What an LNP does
A 2026 review explains that LNPs protect RNA from being broken down, help it escape from the small compartments inside cells (endosomes), and release it where it can act. [1] The same review notes the main limits: immune reactions, limited tissue selectivity, demanding manufacturing and open questions about long-term safety. [1]Non-viral carriers also include polymer particles, other nanomaterials and cell-derived vesicles. A 2026 review says non-viral vectors offer advantages in cargo capacity, flexibility, short-lived expression, potential repeat dosing and avoidance of vector-genome integration, and that ionizable LNPs are currently the most clinically mature non-viral technology. [2] It also lists remaining barriers: endosomal escape, cell-type targeting, delivery beyond the liver and tolerability of repeat doses. [2] This is a review of the field, not a trial.
What is approved
- ONPATTRO (patisiran). An RNA-interference medicine (siRNA) [4] formulated as a lipid complex for delivery to liver cells. [4] The FDA label indicates it for the polyneuropathy (nerve damage) of hereditary transthyretin-mediated amyloidosis in adults. [4] Drugs@FDA records its original approval on August 10, 2018. [5] Approved medicine in the United States for that use. See RNA Interference and siRNA Therapies.
Other RNA drugs reach the liver without LNPs by attaching a sugar-like targeting group (GalNAc) to the RNA. [6][7] Compare with Targeted Delivery and Tissue Specificity and see the full list in Approved Gene and RNA Therapies.
Risks and limits
- Infusion reactions. The ONPATTRO label lists infusion-related reactions as a warning, with monitoring during infusion. [4]
- Nutrient effect. The same label lists reduced serum vitamin A levels, with a label recommendation about vitamin A supplementation. [4]
- Antibodies to the particle. In the ONPATTRO studies, antibodies to a PEG lipid on the particle surface were measured, and anti-drug antibodies developed in 7 of 194 patients (3.6%). [4] Anti-PEG antibodies also occur in healthy people, and a mouse study found that circulating anti-PEG IgM markedly reduced protein production in the liver from an injected mRNA-LNP. [11] That is preclinical, so it cannot be applied directly to people.
- Repeat dosing. Tolerability of repeat doses is listed as an unsolved barrier. [2]
Who should not rely on this
References
- Ganguly SC et al. Targeted delivery of RNA-based therapeutics by lipid nanoparticles. Recent Adv Drug Deliv Formul 2026. PubMed 42817114. Read 2026-10-22.
- Yang Y et al. Recent advances in non-viral vectors for gene therapy and gene delivery: from lipid nanoparticles to engineered extracellular vesicles. Pharmaceutics 2026. PubMed 42797269. Read 2026-10-22.
- Gao P et al. PEGylated lipids in lipid nanoparticle delivery dynamics and therapeutic innovation. Beilstein J Nanotechnol 2025. PubMed 41189930. Read 2026-10-22.
- US FDA prescribing information, ONPATTRO (label data via openFDA). Read 2026-10-22.
- US FDA Drugs@FDA record, ONPATTRO (data via openFDA). Read 2026-10-22.
- US FDA prescribing information, GIVLAARI (label data via openFDA). Read 2026-10-22.
- US FDA prescribing information, LEQVIO (label data via openFDA). Read 2026-10-22.
- Gillmore JD et al. CRISPR-Cas9 in vivo gene editing for transthyretin amyloidosis. N Engl J Med 2021. PubMed 34215024. Read 2026-10-22.
- Musunuru K et al. Patient-specific in vivo gene editing to treat a rare genetic disease. N Engl J Med 2025. PubMed 40373211. Read 2026-10-22.
- Liu Y et al. Overcoming hepatic tropism: precision engineering of lipid nanoparticles for extrahepatic RNA delivery. Mater Today Bio 2026. PubMed 42677161. Read 2026-10-22.
- Abe S et al. Impact of pre-existing anti-polyethylene glycol (PEG) IgM on biodistribution and humoral response of intramuscularly administered PEGylated mRNA loaded lipid nanoparticle. J Control Release 2025. PubMed 40339658. Read 2026-10-22.