Evidence map›Paper›PMID 37317010›Full record

ArticleSmall methods2023

Understanding Intracellular Biology to Improve mRNA Delivery by Lipid Nanoparticles.

Morag Rose Hunter, Lili Cui, Benjamin Thomas Porebski, Sara Pereira, Silvia Sonzini, Uchechukwu Odunze, Preeti Iyer, Ola Engkvist, Rebecca Louise Lloyd, Samantha Peel and 4 more

Abstract read
In one paragraph

Article in Small methods, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed.

  1. Review
  2. Cas12a chRDNA-mediatedMolecular therapy. Nucleic acids · 2026
    Article
  3. Review
  4. Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Machine Learning-Enhanced Nanoparticle Design for Precision Cancer Drug Delivery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. A comprehensive comparison of DNA and RNA vaccines.Advanced drug delivery reviews · 2024
    Review
  17. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Morag Rose HunterAdvanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Cambridge, CB21 6GH, UK.ORCID 0000-0003-1226-9923
Lili CuiAdvanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Cambridge, CB21 6GH, UK.ORCID 0000-0002-0668-2837
Benjamin Thomas PorebskiProtein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK.ORCID 0000-0003-1398-0442
Sara PereiraAdvanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Cambridge, CB21 6GH, UK.
Silvia SonziniAdvanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Cambridge, CB21 6GH, UK.ORCID 0000-0002-7473-546X
Uchechukwu OdunzeAdvanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Cambridge, CB21 6GH, UK.
Preeti IyerMolecular AI, Discovery Sciences, R&D, Astrazeneca, Gothenburg, 431 50, Sweden.
Ola EngkvistMolecular AI, Discovery Sciences, R&D, Astrazeneca, Gothenburg, 431 50, Sweden.ORCID 0000-0003-4970-6461
Rebecca Louise LloydFunctional Genomics, Discovery Sciences, R&D, AstraZeneca, Cambridge, CB4 0WG, UK.
Samantha PeelFunctional Genomics, Discovery Sciences, R&D, AstraZeneca, Cambridge, CB4 0WG, UK.ORCID 0000-0001-9850-1409
Alan SabirshAdvanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Gothenburg, 431 50, Sweden.ORCID 0000-0001-5310-0281
Douglas Ross-ThrieplandFunctional Genomics, Discovery Sciences, R&D, AstraZeneca, Cambridge, CB4 0WG, UK.
Arwyn Tomos JonesCardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, CF10 3NB, UK.ORCID 0000-0003-2781-8905
Arpan Shailesh DesaiAdvanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Cambridge, CB21 6GH, UK.

Funding

Medical Research Council MC_U105178804
6 · The paper itself

Abstract

Poor understanding of intracellular delivery and targeting hinders development of nucleic acid-based therapeutics transported by nanoparticles. Utilizing a siRNA-targeting and small molecule profiling approach with advanced imaging and machine learning biological insights is generated into the mechanism of lipid nanoparticle (MC3-LNP) delivery of mRNA. This workflow is termed Advanced Cellular and Endocytic profiling for Intracellular Delivery (ACE-ID). A cell-based imaging assay and perturbation of 178 targets relevant to intracellular trafficking is used to identify corresponding effects on functional mRNA delivery. Targets improving delivery are analyzed by extracting data-rich phenotypic fingerprints from images using advanced image analysis algorithms. Machine learning is used to determine key features correlating with enhanced delivery, identifying fluid-phase endocytosis as a productive cellular entry route. With this new knowledge, MC3-LNP is re-engineered to target macropinocytosis, and this significantly improves mRNA delivery in vitro and in vivo. The ACE-ID approach can be broadly applicable for optimizing nanomedicine-based intracellular delivery systems and has the potential to accelerate the development of delivery systems for nucleic acid-based therapeutics.

Indexed as

EndocytosisNanoparticlesBiologyLiposomesRNA, MessengerLipid NanoparticlesLiposomesRNA, Messengerdrug deliveryintracellular traffickinglipid nanoparticlesmachine learningnucleic acid therapeutics

Identifiers

PMID37317010
PMCPMC7615154

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.