ArticleNature communications2022
Piperazine-derived lipid nanoparticles deliver mRNA to immune cells in vivo.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
79 citing papers in PubMed, 167 citations in OpenAlex.
- Engineering lipid nanoparticle surface hydrophobicity to modulate nano-bio interface and enable tissue-selective mRNA delivery.Biomaterials · 2026Article
- Structural evolution of ionizable lipids for nucleic acid delivery.Nature reviews. Chemistry · 2026Review
- Combinatorial synthesis of novel polycations for mRNA deliveryRSC applied polymers · 2026Article
- Preparation of placenta-tropic mRNA lipid nanoparticles for pregnancy disorders.Nature protocols · 2026Review
- Preparation of targeted lipid nanoparticles for precision nucleic acid delivery.Nature protocols · 2026Review
- Advancements of mRNA-lipid nanoparticle links to gene editing and immune responses.Journal, genetic engineering & biotechnology · 2026Review
- Non-invasive nanoparticle barcoding in nonhuman primates.Nature biotechnology · 2026Article
- Delivering the future of immunotherapy: A state-of-the-art review of gene editing in immune cells with lipid nanoparticles.Materials today. Bio · 2026Review
- Delivery Systems for Therapeutic Genome Editing: Challenges, Innovations, and Future Perspectives.MedComm · 2026Review
- Decoding Undesirable Inflammatory Responses of Nucleic Acid-Delivering Lipid Nanoparticles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Helper lipid-engineered extracellular vesicles enable PET imaging-guided pulmonary siRNA delivery to treat lung metastasis.Science advances · 2026Article
- Lipid nanoparticle screening in nonhuman primates with minimal loss of life.Nature biotechnology · 2026Article
- Thioester-Containing Ionizable Lipids with Enhanced Endosomal Escape and Biodegradability for mRNA and tRNA Delivery.Pharmaceutics · 2026Article
- Lipid Nanoparticles for Delivery of CRISPR Gene Editing Components.Small methods · 2026Review
- Life history enlightened therapies: cell cycle mapping to identify molecular targets to prevent hepatocellular carcinoma.Evolution, medicine, and public health · 2026Article
- Rational design and applications of piperazine and cyclohexane ionizable lipids for PKU and SSADH deficiency.Molecular therapy. Nucleic acids · 2025Article
- Glycolipid nanoparticles target the spleen and detarget the liver without charge.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Lipid nanoparticle-mediated mRNA delivery to CD34Nature biotechnology · 2025Article
- High-Throughput Strategies for Streamlining Lipid Nanoparticle Development Pipeline.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Anionic lipids modulate mRNA-lipid nanoparticle immunogenicity and confer protection in a mouse model of multiple sclerosis.bioRxiv : the preprint server for biology · 2025Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 2 countries.
Funding
Abstract
In humans, lipid nanoparticles (LNPs) have safely delivered therapeutic RNA to hepatocytes after systemic administration and to antigen-presenting cells after intramuscular injection. However, systemic RNA delivery to non-hepatocytes remains challenging, especially without targeting ligands such as antibodies, peptides, or aptamers. Here we report that piperazine-containing ionizable lipids (Pi-Lipids) preferentially deliver mRNA to immune cells in vivo without targeting ligands. After synthesizing and characterizing Pi-Lipids, we use high-throughput DNA barcoding to quantify how 65 chemically distinct LNPs functionally delivered mRNA (i.e., mRNA translated into functional, gene-editing protein) in 14 cell types directly in vivo. By analyzing the relationships between lipid structure and cellular targeting, we identify lipid traits that increase delivery in vivo. In addition, we characterize Pi-A10, an LNP that preferentially delivers mRNA to the liver and splenic immune cells at the clinically relevant dose of 0.3 mg/kg. These data demonstrate that high-throughput in vivo studies can identify nanoparticles with natural non-hepatocyte tropism and support the hypothesis that lipids with bioactive small-molecule motifs can deliver mRNA in vivo.
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What OpenQuestion holds
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.