Evidence map›Paper›PMID 42283697›Full record

ArticleACS nano2026

Storage Buffer Composition Impacts Internal Structure, Freeze-Thaw Stability, and Transfection Efficiency of mRNA-Lipid Nanoparticles.

Meysam Mohammadi-Zerankeshi, Dylan J Charland, Keira A Donnelly, Geoffrey T Nash, Jiale Shi, Dipak N Patil, Julia Ennis, Kenneth G Rodriguez, Sonia Corba, Noah A Wambolt and 10 more

Abstract read
In one paragraph

Article in ACS nano, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

20 authors.

Meysam Mohammadi-ZerankeshiWalker Department of Mechanical Engineering, University of Texas at Austin, Austin, Texas 78712, United States.ORCID 0000-0003-0851-2644
Dylan J CharlandLilly Seaport Innovation Center, Boston, Massachusetts 02210, United States.
Keira A DonnellyDepartment of Biomedical Engineering, University of Texas at Austin, Austin, Texas 78712, United States.
Geoffrey T NashEli Lilly and Company, Indianapolis, Indiana 46225, United States.ORCID 0000-0002-1470-2279
Jiale ShiDepartment of Chemistry, Boston University, Boston, Massachusetts 02215, United States.ORCID 0000-0002-5447-3925
Dipak N PatilEli Lilly and Company, Indianapolis, Indiana 46225, United States.
Julia EnnisLilly Seaport Innovation Center, Boston, Massachusetts 02210, United States.
Kenneth G RodriguezLilly Seaport Innovation Center, Boston, Massachusetts 02210, United States.ORCID 0009-0007-9444-5367
Sonia CorbaEurofins PSS Insourcing Solutions, LLC, Lancaster, Pennsylvania 17601, United States.
Noah A WamboltEurofins PSS Insourcing Solutions, LLC, Lancaster, Pennsylvania 17601, United States.
Haocheng ChuehLilly Seaport Innovation Center, Boston, Massachusetts 02210, United States.
Khaled AboulFotouhWalker Department of Mechanical Engineering, University of Texas at Austin, Austin, Texas 78712, United States.ORCID 0000-0002-2554-5483
Mohammed R KawelahMcKetta Department of Chemical Engineering, University of Texas at Austin, Austin, Texas 78712, United States.ORCID 0009-0003-0462-9383
Younghoon OhLilly Seaport Innovation Center, Boston, Massachusetts 02210, United States.
Dennis YangEli Lilly and Company, Indianapolis, Indiana 46225, United States.
Ken K QianEli Lilly and Company, Indianapolis, Indiana 46225, United States.ORCID 0000-0002-1942-1943
Qiang CuiDepartment of Chemistry, Boston University, Boston, Massachusetts 02215, United States.ORCID 0000-0001-6214-5211
Keith P JohnstonMcKetta Department of Chemical Engineering, University of Texas at Austin, Austin, Texas 78712, United States.ORCID 0000-0002-0915-1337
Daniel A EstabrookLilly Seaport Innovation Center, Boston, Massachusetts 02210, United States.
Alexander E MarrasWalker Department of Mechanical Engineering, University of Texas at Austin, Austin, Texas 78712, United States.ORCID 0000-0001-8972-9532

Funding

Expanding the design space of polyelectrolyte complex micellesR35GM154984 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI Alexander Edison Marras · 2024 to 2026
$1.1M
NIGMS NIH HHS R35 GM154984
6 · The paper itself

Abstract

Messenger RNA (mRNA) lipid nanoparticles (mRNA-LNPs) are central to emerging vaccines and therapeutics, but their wide implementation is constrained by limited endosomal escape and instability during long-term storage and freezing. While buffers are routinely optimized to prevent instability, the impact of buffer on the internal structural organization of LNPs and, consequently, their delivery efficiency remain unresolved. Here, we study the impact of storage in Tris, histidine, and citrate buffers for mRNA-LNPs formulated with LP-01, MC3, and SM-102 ionizable lipids. We demonstrate that storage buffer identity and concentration govern mRNA-LNP internal ordering before and after freeze-thaw and are thus critical parameters for engineering high-performance formulations. Deconvoluting ordered phases into an mRNA-lipid region and excess lipid region reveals the importance of excess ionizable lipid behavior in enhancing endosomal escape. Prior to freezing, citrate buffer enhances transfection efficiency by promoting a transition to the fusogenic inverse hexagonal (H

Indexed as

LipidsNanoparticlesRNA, MessengerTransfectionBuffersFreezingHumansLiposomesParticle SizeBuffersLipid NanoparticlesLipidsLiposomesRNA, Messengerbuffer effectsformulation developmentionizable lipidsmolecular dynamicsmRNA lipid nanoparticlesRNA deliverySAXS

Identifiers

PMID42283697
PMCPMC13325854

What OpenQuestion holds

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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.