Evidence map›Paper›PMID 34904974›Full record

ArticleBiomaterials science2022

Optimization of phospholipid chemistry for improved lipid nanoparticle (LNP) delivery of messenger RNA (mRNA).

Ester Álvarez-Benedicto, Lukas Farbiak, Martha Márquez Ramírez, Xu Wang, Lindsay T Johnson, Osamah Mian, Erick D Guerrero, Daniel J Siegwart

Open access · greenAbstract read
In one paragraph

Article in Biomaterials science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.

0numbers the graph read from it
0cells of the map it votes in
100citing papers in PubMed
8.4field-weighted citation impact, top 1% of its field
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

100 citing papers in PubMed, 195 citations in OpenAlex.

  1. Article
  2. RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026
    Review
  3. Review
  4. Article
  5. Review
  6. The RNA delivery dilemma-lipid versus polymer nanoparticle platforms.Drug delivery and translational research · 2026
    Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Review
  12. Optimizing C14120-based LNPs forMolecular therapy. Nucleic acids · 2026
    Article
  13. Article
  14. Characterizing the Impact of the Cell Cycle on mRNA Lipid Nanoparticles.Journal of the American Chemical Society · 2026
    Article
  15. Optimizing mRNA delivery with targeted elastin-like polypeptide-based LENN formulations: Insights into the endocytosis mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article

40 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

8 authors at 1 institution in 1 country.

Ester Álvarez-BenedictoDepartment of Biochemistry, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. Daniel.Siegwart@UTSouthwestern.edu.
Lukas FarbiakDepartment of Biochemistry, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. Daniel.Siegwart@UTSouthwestern.edu.
Martha Márquez RamírezDepartment of Biochemistry, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. Daniel.Siegwart@UTSouthwestern.edu.
Xu WangDepartment of Biochemistry, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. Daniel.Siegwart@UTSouthwestern.edu.
Lindsay T JohnsonDepartment of Biochemistry, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. Daniel.Siegwart@UTSouthwestern.edu.ORCID http://orcid.org/0000-0002-4563-5486
Osamah MianDepartment of Biochemistry, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. Daniel.Siegwart@UTSouthwestern.edu.ORCID http://orcid.org/0000-0001-7039-0081
Erick D GuerreroDepartment of Biochemistry, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. Daniel.Siegwart@UTSouthwestern.edu.ORCID http://orcid.org/0000-0002-2076-3537
Daniel J SiegwartDepartment of Biochemistry, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. Daniel.Siegwart@UTSouthwestern.edu.ORCID http://orcid.org/0000-0003-3823-1931
The University of Texas Southwestern Medical Center · US

Funding

UT Southwestern Medical Center Simmons Comprehensive Cancer CenterP30CA142543 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Sandi Leigh Pruitt · 2010 to 2026
$53.7M
Defining the molecular interactions within nanoparticles that enable delivery of long nucleic acidsR01EB025192 · NIBIB · UT SOUTHWESTERN MEDICAL CENTER · PI SIEGWART, DANIEL JOHN · 2018 to 2025
$3.1M
NCI NIH HHS P30 CA142543NIBIB NIH HHS R01 EB025192
6 · The paper itself

Abstract

Lipid nanoparticles (LNPs) have been established as an essential platform for nucleic acid delivery. Efforts have led to the development of vaccines that protect against SARS-CoV-2 infection using LNPs to deliver messenger RNA (mRNA) coding for the viral spike protein. Out of the four essential components that comprise LNPs, phospholipids represent an underappreciated opportunity for fundamental and translational study. We investigated this avenue by systematically modulating the identity of the phospholipid in LNPs with the goal of identifying specific moieties that directly enhance or hinder delivery efficacy. Results indicate that phospholipid chemistry can enhance mRNA delivery by increasing membrane fusion and enhancing endosomal escape. Phospholipids containing phosphoethanolamine (PE) head groups likely increase endosomal escape due to their fusogenic properties. Additionally, it was found that zwitterionic phospholipids mainly aided liver delivery, whereas negatively charged phospholipids changed the tropism of the LNPs from liver to spleen. These results demonstrate that the choice of phospholipid plays a role intracellularly by enhancing endosomal escape, while also driving organ tropism

Indexed as

COVID-19NanoparticlesHumansLiposomesPhospholipidsRNA, MessengerRNA, Small InterferingSARS-CoV-2Lipid NanoparticlesLiposomesPhospholipidsRNA, MessengerRNA, Small Interfering

Identifiers

PMID34904974
PMCPMC9113778
OpenAlexW3217272213

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.