Evidence map›Paper›PMID 41845088›Full record

ArticleNature biomedical engineering2026

'Tripod-like' lung-targeting (LuT) lipids for highly efficient and selective LNPs for gene delivery and editing.

Zeru Tian, Xu Wang, Sumanta Chatterjee, William Miller, Erick Guerrero, Yun-Chieh Sung, Alexis Pacheco Benitez, Sean Dilliard, Xiaoyan Bian, Amogh Vaidya and 10 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature biomedical engineering, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. International journal of biological sciences · 2026
    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.

Zeru Tian *Department of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Xu Wang *Department of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0002-8925-5645
Sumanta ChatterjeeDepartment of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
William MillerDepartment of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0002-6096-0711
Erick GuerreroDepartment of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Yun-Chieh SungDepartment of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Alexis Pacheco BenitezDepartment of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Sean DilliardDepartment of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Xiaoyan BianDepartment of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Amogh VaidyaDepartment of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0003-0712-659X
Xizhen LianDepartment of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Stephen MooreDepartment of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Yehui SunDepartment of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0003-0215-6095
Minjeong KimDepartment of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Yufen XiaoDepartment of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0002-5604-7479
Shiying WuDepartment of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0002-6902-9544
Bret M EversDepartment of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0001-5686-0315
Jeon LeeLyda Hill Department of Bioinformatics, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Lukas FarbiakDepartment of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0003-4107-1676
Daniel J SiegwartDepartment of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX, USA. Daniel.Siegwart@UTSouthwestern.edu.ORCID http://orcid.org/0000-0003-3823-1931

Funding

U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA269787-01U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB) 5R01EB025192-06Welch Foundation I-2123-20220031
6 · The paper itself

Abstract

Developing lung-targeting delivery systems is essential for treating pulmonary conditions such as genetic respiratory diseases, infections, fibrosis and cancer. We synthesized and evaluated 444 lung-targeting lipids (LuT lipids) that form lipid nanoparticles (LNPs) to efficiently deliver messenger RNA and CRISPR-Cas9 genome editors to lungs with minimal side effects. Empirical analyses revealed structure-activity relationships, with top-performing LuT lipids possessing a unique 'tripod-like' structure consisting of a quaternary amine head, three long alkyl chains as legs and a short chain as a handle. LuT lipids improved endosomal escape, cargo release and endogenous targeting via adsorption of plasma proteins. Lead 1A7B13 LNPs showed a 25.5-fold improvement in mRNA delivery and a 9.2-fold increase in CRISPR-Cas9 gene-editing efficiency compared to benchmark DOTAP SORT LNPs, achieving over 90% selectivity to the lungs. 1A7B13 LNPs effectively delivered IL-10 mRNA in a therapeutic model of acute lung injury. This study reveals the relationship between lipid structure and lung-targeting activity, enriching the toolkit for lung-specific carriers.

Identifiers

PMID41845088

What OpenQuestion holds

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Registered trials

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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.