ArticleNature biotechnology2026
Safer non-viral DNA delivery using lipid nanoparticles loaded with endogenous anti-inflammatory lipids.
Article in Nature biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed.
- Bioactive lipid-derived nanoparticles for RNA delivery.Materials today (Kidlington, England) · 2026Article
- Gene editing using large insertions.Nature biotechnology · 2026Article
- mRNA delivery to the retina restores REP1 function in choroideremia.Molecular therapy. Advances · 2026Article
- Charge-switching ionizable lipids lower the toxicity of lipid nanoparticles.Nature nanotechnology · 2026Article
- Focused ultrasound-mediated lipid nanoparticle delivery for brain gene editing.Molecular therapy. Nucleic acids · 2026Article
- Double-stranded DNA donors and CRISPR-Cas9 for universal correction of mutations causing cystic fibrosis in human airway cells.Molecular therapy. Nucleic acids · 2026Article
- Nucleic acid sensing pathways in kidney disease development.Nature reviews. Nephrology · 2026Review
- Delivering the future of immunotherapy: A state-of-the-art review of gene editing in immune cells with lipid nanoparticles.Materials today. Bio · 2026Review
- In situ generation of proinflammatory CAR macrophages via mRNA-TLR agonist co-delivery for triple-negative breast cancer immunotherapy.Journal for immunotherapy of cancer · 2026Article
- Peptide additives reprogram the lipid nanoparticle corona and enhance gene delivery in a serum-free environment for lung epithelium.bioRxiv : the preprint server for biology · 2026Article
- Therapeutic targeting of the cGAS-STING pathway in human disease.The Journal of clinical investigation · 2026Review
- Ethosomal nanocarriers for enhanced skin drug delivery: a comprehensive review.Molecular biology reports · 2026Review
- Antioxidant lipid nanoparticles enhance mRNA stability for regeneration therapy and gene editing.Nature communications · 2026Article
- From LNPs to hybrid nanocarriers: development, challenges and redesign of non-viral gene delivery.Journal of nanobiotechnology · 2026Review
- The senescence-inhibitory p53 isoform Δ133p53α: enhancing cancer immunotherapy and exploring novel therapeutic approaches for senescence-associated diseases.GeroScience · 2026Review
- Localized NF-κB Inhibition Reduces Lipid Nanoparticle-Associated Inflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Engineering challenges and translational opportunities in emerging gene delivery platforms.Nature biomedical engineering · 2026Review
- Decoding Undesirable Inflammatory Responses of Nucleic Acid-Delivering Lipid Nanoparticles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Recent Developments in Lipid Nanoparticle-Mediated Delivery of Biotherapeutics and Gene Therapy Across the Blood-Brain Barrier.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- A low-toxicity circular single-stranded DNA platform for safe and potent IL-12 immunotherapy against hepatocellular carcinoma.Journal of nanobiotechnology · 2026Article
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Authors and funding
15 authors.
Funding
Abstract
The value of lipid nanoparticles (LNPs) for delivery of messenger RNA (mRNA) was demonstrated by the coronavirus disease 2019 (COVID-19) mRNA vaccines, but the ability to use LNPs to deliver plasmid DNA (pDNA) would provide additional advantages, such as longer-term expression and availability of promoter sequences. However, pDNA-LNPs face substantial challenges, such as toxicity and low delivery efficiency. Here we show that pDNA-LNPs induce acute inflammation in naive mice that is primarily driven by the cGAS-STING pathway. Inspired by DNA viruses that inhibit this pathway for replication, we loaded endogenous lipids that inhibit STING into pDNA-LNPs. Loading nitro-oleic acid (NOA) into pDNA-LNPs (NOA-pDNA-LNPs) ameliorated serious inflammatory responses in vivo, enabling safer, prolonged transgene expression-11.5 times greater than that of mRNA-LNPs at day 32. Additionally, we performed a small LNP formulation screen to iteratively optimize transgene expression and increase expression 50-fold in vitro. pDNA-LNPs loaded with NOA and other bioactive molecules should advance genetic medicine by enabling longer-term and promoter-controlled transgene expression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.