Evidence map›Paper›PMID 40069324›Full record

ReviewNature protocols2025

mRNA lipid nanoparticle formulation, characterization and evaluation.

Yutian Ma, Rachel VanKeulen-Miller, Owen S Fenton

Abstract readReview
In one paragraph

Review in Nature protocols, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing 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

37 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Messenger RNA and guide RNA distributions in lipid nanoparticles impact gene-editing efficiency in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Impact of ionizable lipid source on quality and stability of siRNA-loaded lipid nanoparticles.Journal of controlled release : official journal of the Controlled Release Society · 2026
    Article
  19. Article
  20. 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

3 authors.

Yutian MaDivision of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Rachel VanKeulen-MillerDepartment of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Owen S FentonDivision of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. osfenton@unc.edu.

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
UNC Neuroscience Center Research Cores: MicroscopyP30NS045892 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ZYLKA, MARK J. · 2003 to 2022
$11.5M
Preclinical CoreP50HD103573 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI GABRIEL S DICHTER · 2020 to 2026
$9.7M
CTSA K12 Program at UNCK12TR004416 · NCATS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Michelle Hernandez, Jonathan J Juliano · 2023 to 2026
$6.5M
Investigating and Manipulating Cells in Low Oxygen Environments Using Lipid NanoparticlesR35GM157060 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Owen S Fenton · 2025 to 2026
$764k
Optimization of Tannic Acid Lipid Nanoparticles for a Therapeutic mRNA Vaccine Against MelanomaR21EB034942 · NIBIB · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FENTON, OWEN S · 2023 to 2025
$601k
Zeiss LSM 980 Confocal MicroscopeS10OD032388 · OD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ITANO, MICHELLE S · 2022 to 2022
$597k
NCATS NIH HHS K12 TR004416NCI NIH HHS P30 CA016086NIBIB NIH HHS R21 EB034942NICHD NIH HHS P50 HD103573NIGMS NIH HHS R35 GM157060NIH HHS S10 OD032388NINDS NIH HHS P30 NS045892U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS) 1K12TR004416-01U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB) 1R21EB034942-01
6 · The paper itself

Abstract

mRNA-based therapies have emerged as a cutting-edge approach for diverse therapeutic applications. However, substantial barriers exist that hinder scientists from entering this research field, including the technical complexity and multiple potential workflows available for formulating and evaluating mRNA lipid nanoparticles (LNPs). Here we present an easy-to-follow and step-by-step guide for mRNA LNP formulation, characterization and in vitro and in vivo evaluation that could lower these barriers, facilitating entry for scientists in academia, industry and clinical settings into this research space. In this protocol, we detail steps for formulating representative mRNA LNPs (0.5 d) and characterizing key parameters (1-6 d) such as size, polydispersity index, zeta potential, mRNA concentration, mRNA encapsulation efficiency and stability. Then, we describe in vitro evaluations (3-6 d), such as protein expression, cell uptake and mechanism investigations (3-5 d), including endosomal escape, as well as in vivo delivery evaluation (2-3 d) encompassing intracellular and secreted protein expression levels, biodistribution and additional tolerability studies (1-2 weeks). Unlike some alternative protocols that may focus on discrete aspects of the workflow-such as formulation, characterization or evaluation-our protocol instead aims to integrate each of these aspects into a simplified, singular workflow applicable across multiple types of mRNA LNP formulations. In describing these procedures, we wish to disseminate one potential workflow for mRNA LNP production and evaluation, with the ultimate goal of furthering innovation, collaboration and the translational advancement of mRNA LNPs.

Indexed as

LipidsNanoparticlesRNA, MessengerAnimalsHumansLiposomesMiceLipid NanoparticlesLipidsLiposomesRNA, Messenger

Identifiers

PMID40069324
PMCPMC12312782

What OpenQuestion holds

Textmetadata
LicenceTDM
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.