Publication

High-throughput screens identify a lipid nanoparticle that preferentially delivers mRNA to human tumors in vivo

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Last modified
  • 07/07/2026
Type of Material
Authors
    Sebastian G. Huayamares, Georgia Institute of TechnologyMelissa P. Lokugamage, Georgia Institute of TechnologyRegina Rab, Emory UniversityAlejandro J. Da Silva Sanchez, Georgia Institute of TechnologyHyejin Kim, Georgia Institute of TechnologyAfsane Radmand, Georgia Institute of TechnologyDavid Loughrey, Georgia Institute of TechnologyLiming Lian, Georgia Institute of TechnologyYuning Hou, Emory UniversityBhagelu R. Achyut, Emory UniversityAnnette Ehrhardt, Emory UniversityJeong S. Hong, Emory UniversityCory D. Sago, Georgia Institute of TechnologyKalina Paunovska, Georgia Institute of TechnologyElisa Schrader Echeverri, Georgia Institute of TechnologyDaryll Vanover, Georgia Institute of TechnologyPhilip J. Santangelo, Georgia Institute of TechnologyEric J. Sorcher, Emory UniversityJames E. Dahlman, Georgia Institute of Technology
Language
  • English
Date
  • 2023-04-12
Publisher
  • Elsevier
Publication Version
Copyright Statement
  • © 2023 Elsevier B.V. All rights reserved.
License
Final Published Version (URL)
Title of Journal or Parent Work
Volume
  • 357
Start Page
  • 394
End Page
  • 403
Grant/Funding Agency
  • National Institutes of Health
Grant/Funding Information
  • This research was funded by the National Institutes of Health (R01DE026941, awarded to E.J.S. and J.E.D.).
Supplemental Material (URL)
Abstract
  • Lipid nanoparticles (LNPs) are a clinically relevant way to deliver therapeutic mRNA to hepatocytes in patients. However, LNP-mRNA delivery to end-stage solid tumors such as head and neck squamous cell carcinoma (HNSCC) remains more challenging. While scientists have used in vitro assays to evaluate potential nanoparticles for HNSCC delivery, high-throughput delivery assays performed directly in vivo have not been reported. Here we use a high-throughput LNP assay to evaluate how 94 chemically distinct nanoparticles delivered nucleic acids to HNSCC solid tumors in vivo. DNA barcodes were used to identify LNPHNSCC, a novel LNP for systemic delivery to HNSCC solid tumors. Importantly, LNPHNSCC retains tropism to HNSCC solid tumors while minimizing off-target delivery to the liver.
Author Notes
  • Acknowledgements: The authors thank Karen Tiegren at Georgia Tech for copyediting the manuscript.
  • Author contributions: Sebastian G. Huayamares: Conceptualization, Methodology, Validation, Investigation, Writing – Original Draft. Melissa P. Lokugamage: Conceptualization, Methodology, Investigation, Writing – Original Draft. Regina Rab: Methodology, Investigation. Alejandro Da Silva: Investigation. Hyejin Kim: Investigation. Afsane Radmand: Investigation. David Loughrey: Investigation. Liming Lian: Investigation. Yuning Hou: Investigation. Bhagelu R. Achyut: Investigation. Annette Ehrhardt: Investigation. Jeong S. Hong: Investigation. Cory D. Sago: Investigation. Kalina Paunovska: Investigation. Elisa Schrader Echeverri: Investigation. Daryll Vanover: Investigation. Philip J. Santangelo: Supervision. Eric J. Sorscher: Conceptualization, Methodology, Supervision, Writing – Review & Editing, Project Administration. James E. Dahlman: Conceptualization, Methodology, Supervision, Writing – Review & Editing.
  • Competing interests: J.E.D. is an advisor to GV. E.J.S. has ownership interest in PNP Therapeutics, Inc. and serves on the Board of Directors for the company, which develops products used in cancer research. Dr. Sorscher is also an inventor of technology being evaluated in studies described by this report. The terms of this arrangement for Dr. Sorscher have been reviewed and approved by Emory University in accordance with its conflict-of-interest policies. Dr. Jeong Hong also has minor equity interest in this company. All other authors declare no conflict of interest.
  • Author contributions: S.G.H., M.P.L., E.J.S., and J.E.D. designed experiments. All authors helped perform the experiments. S.G.H., M.P.L., E.J.S., and J.E.D. analyzed data. S.G.H., M.P.L., E.J.S., and J.E.D. wrote the article, which was reviewed by all other authors.
  • Correspondence: Eric J. Sorcher, esorscher@emory.edu, James E. Dahlam, james.dahlman@bme.gatech.edu
Keywords
Subject - Topics
  • Tumors
  • Cancer
  • Lipids

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