Evidence map›Paper›PMID 37556502›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2023

Throughput-scalable manufacturing of SARS-CoV-2 mRNA lipid nanoparticle vaccines.

Sarah J Shepherd, Xuexiang Han, Alvin J Mukalel, Rakan El-Mayta, Ajay S Thatte, Jingyu Wu, Marshall S Padilla, Mohamad-Gabriel Alameh, Neha Srikumar, Daeyeon Lee and 3 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing 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

64 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. Post-loading ribonucleic acid into lipid nanoparticle carriers.bioRxiv : the preprint server for biology · 2026
    Article
  8. Review
  9. Review
  10. Review
  11. Review
  12. Article
  13. Emerging strategies to reduce the side effects of CAR-T cell therapy: focusing on gene editing and nanotechnology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Review
  19. Review
  20. Nanovaccines for lung cancer: Platforms, mechanistic insights, and translational challenges.Chinese medical journal pulmonary and critical care medicine · 2026
    Review

4 more citing papers are in PubMed but not listed here.

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

13 authors.

Sarah J ShepherdDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104.
Xuexiang HanDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104.
Alvin J MukalelDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104.
Rakan El-MaytaDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104.ORCID 0000-0002-5855-233X
Ajay S ThatteDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104.
Jingyu WuDepartment of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104.
Marshall S PadillaDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104.
Mohamad-Gabriel AlamehDepartment of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Neha SrikumarDepartment of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Daeyeon LeeDepartment of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104.
Drew WeissmanDepartment of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
David Issadore *Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104.
Michael J Mitchell *Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104.ORCID 0000-0002-3628-2244

Funding

Center for Sub-Cellular GenomicsRM1HG010023 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI EBERWINE, JAMES H, KIM, JUNHYONG · 2018 to 2022
$11.0M
In utero gene editing to cure a metabolic liver diseaseR01DK123049 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI PERANTEAU, WILLIAM H. · 2020 to 2024
$3.7M
Targeting stem-like cells and their niche in pancreatic cancerR37CA244911 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Tuomas Tammela · 2020 to 2026
$3.4M
Structural biology and molecular biophysics training programT32GM132039 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI Ben E. Black, Elizabeth Rhoades · 2019 to 2026
$3.3M
Engineered Granular Hydrogels for Endogenous Tissue RepairR01HL160616 · NHLBI · UNIVERSITY OF COLORADO · PI BURDICK, JASON A · 2022 to 2025
$2.5M
A data-driven drug delivery (4D) platform for probing and treating the chemoresistant bone marrow microenvironmentDP2TR002776 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL, MICHAEL J · 2018 to 2018
$2.4M
Modular approach for the delivery of antibodies into the cytoplasm of cellsR01CA241661 · NCI · UNIVERSITY OF PENNSYLVANIA · PI TSOURKAS, ANDREW · 2019 to 2023
$1.8M
Advanced Training at the Interface of Engineering and Oral-Craniofacial SciencesT90DE030854 · NIDCR · UNIVERSITY OF PENNSYLVANIA · PI Hyun Koo, Kathleen J Stebe · 2021 to 2026
$1.4M
High Throughput Digital Droplet ELISA for Ultrasensitive Multiplexed DiagnosticsR21CA236653 · NCI · UNIVERSITY OF PENNSYLVANIA · PI ISSADORE, DAVID AARON · 2020 to 2022
$578k
NCATS NIH HHS DP2 TR002776NCI NIH HHS R01 CA241661NCI NIH HHS R21 CA236653NCI NIH HHS R37 CA244911NHGRI NIH HHS RM1 HG010023NHLBI NIH HHS R01 HL160616NIDCR NIH HHS T90 DE030854NIDDK NIH HHS R01 DK123049NIGMS NIH HHS T32 GM132039
6 · The paper itself

Abstract

Lipid nanoparticles (LNPs) are a potent delivery technology that have made it possible for the recent clinical breakthroughs in mRNA therapeutics and vaccines. A key challenge to the broader implementation of mRNA therapeutics and vaccines is the development of technology to produce precisely defined LNP formulations, with throughput that can scale from discovery to commercial manufacturing and meet the stringent manufacturing standards of the pharmaceutical industry. To address these challenges, we have developed a microfluidic chip that incorporates 1×, 10×, or 256× LNP-generating units that achieve scalable production rates of up to 17 L/h of precisely defined LNPs. Using these chips, we demonstrate that LNP physical properties and potency in vivo are unchanged as throughput is scaled. Our chips are fabricated out of silicon and glass substrates, which have excellent solvent compatibility, compatibility with pharmaceutical manufacturing, and can be fully reset and reused. SARS-CoV-2 mRNA-LNP vaccines formulated by our chips triggered potent antibody responses in a preclinical study. These results demonstrate the feasibility of directly translating microfluidic-generated LNPs to the scale necessary for commercial production.

Indexed as

COVID-19NanoparticlesHumansLiposomesRNA, MessengerSARS-CoV-2Lipid NanoparticlesLiposomesRNA, Messengerdrug deliverymRNAnanomedicinenanoparticlevaccines

Identifiers

PMID37556502
PMCPMC10438381

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.