ArticleScience advances2020
Increased PIP3 activity blocks nanoparticle mRNA delivery.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- PI3K/AKT signaling pathway: molecular crossroads in tumorigenesis and therapeutic innovation.Signal transduction and targeted therapy · 2026Review
- Optimization of a Dissolvable Lipid Nanoparticle Microneedle Formulation for mRNA Delivery Using Design of Experiments.ACS applied materials & interfaces · 2025Article
- Evaluating cell cycle- and autophagy-associated cellular accumulation of lipid-based nanoparticles.Nature communications · 2025Article
- From structural design to delivery: mRNA therapeutics for cancer immunotherapy.Exploration (Beijing, China) · 2024Review
- Digital Barcodes for High-Throughput Screening.Chem & bio engineering · 2024Review
- Interferon-inducible phospholipids govern IFITM3-dependent endosomal antiviral immunity.The EMBO journal · 2023Article
- Regulatory circular RNAs in viral diseases: applications in diagnosis and therapy.RNA biology · 2023Review
- The landscape of mRNA nanomedicine.Nature medicine · 2022Review
- Nanoparticle single-cell multiomic readouts reveal that cell heterogeneity influences lipid nanoparticle-mediated messenger RNA delivery.Nature nanotechnology · 2022Article
- Recent advances in lipid nanoparticles for delivery of nucleic acid, mRNA, and gene editing-based therapeutics.Drug metabolism and pharmacokinetics · 2022Review
- Drug delivery systems for RNA therapeutics.Nature reviews. Genetics · 2022Review
- Therapeutic RNA Delivery for COVID and Other Diseases.Advanced healthcare materials · 2021Review
- Whither COVID-19 vaccines?Nature biotechnology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The biological pathways that affect drug delivery in vivo remain poorly understood. We hypothesized that altering cell metabolism with phosphatidylinositol (3,4,5)-triphosphate (PIP3), a bioactive lipid upstream of the metabolic pathway PI3K (phosphatidylinositol 3-kinase)/AKT/ mTOR (mammalian target of rapamycin) would transiently increase protein translated by nanoparticle-delivered messenger RNA (mRNA) since these pathways increase growth and proliferation. Instead, we found that PIP3 blocked delivery of clinically-relevant lipid nanoparticles (LNPs) across multiple cell types in vitro and in vivo. PIP3-driven reductions in LNP delivery were not caused by toxicity, cell uptake, or endosomal escape. Interestingly, RNA sequencing and metabolomics analyses suggested an increase in basal metabolic rate. Higher transcriptional activity and mitochondrial expansion led us to formulate two competing hypotheses that explain the reductions in LNP-mediated mRNA delivery. First, PIP3 induced consumption of limited cellular resources, "drowning out" exogenously-delivered mRNA. Second, PIP3 triggers a catabolic response that leads to protein degradation and decreased translation.
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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.