Evidence map›Paper›PMID 42489054›Full record

ArticleSmall (Weinheim an der Bergstrasse, Germany)2026

Hydrophobic Tail and Linker Diversification of PEG-Lipids Unlocks Precise Muscle Tropism of mRNA-Lipid Nanoparticles.

Bingqian Ou, Xuying Tang, Sunxiang Qian, Bo Chen, Sisi Fang, Jinshuang Su, Xiaopeng Sheng, Jie Feng, Zhefan Yuan, Jing Zhang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Small (Weinheim an der Bergstrasse, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Bingqian OuState Key Laboratory of Advanced Separation Membrane Materials, Zhejiang Key Laboratory of Advanced Polymer Materials Modification and Application Technology, College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou, P. R. China.
Xuying TangState Key Laboratory of Advanced Separation Membrane Materials, Zhejiang Key Laboratory of Advanced Polymer Materials Modification and Application Technology, College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou, P. R. China.
Sunxiang QianCybernaX Biotechnologies, Hangzhou, Zhejiang, P. R. China.
Bo ChenCybernaX Biotechnologies, Hangzhou, Zhejiang, P. R. China.
Sisi FangState Key Laboratory of Advanced Separation Membrane Materials, Zhejiang Key Laboratory of Advanced Polymer Materials Modification and Application Technology, College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou, P. R. China.
Jinshuang SuState Key Laboratory of Advanced Separation Membrane Materials, Zhejiang Key Laboratory of Advanced Polymer Materials Modification and Application Technology, College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou, P. R. China.
Xiaopeng ShengState Key Laboratory of Advanced Separation Membrane Materials, Zhejiang Key Laboratory of Advanced Polymer Materials Modification and Application Technology, College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou, P. R. China.
Jie FengState Key Laboratory of Advanced Separation Membrane Materials, Zhejiang Key Laboratory of Advanced Polymer Materials Modification and Application Technology, College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou, P. R. China.
Zhefan YuanCybernaX Biotechnologies, Hangzhou, Zhejiang, P. R. China.
Jing ZhangState Key Laboratory of Advanced Separation Membrane Materials, Zhejiang Key Laboratory of Advanced Polymer Materials Modification and Application Technology, College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou, P. R. China.

Funding

National Natural Science Foundation of China 52073256
6 · The paper itself

Abstract

Intramuscular mRNA lipid nanoparticles (LNPs) often exhibit undesirable liver accumulation, compromising safety and efficacy. While optimization efforts focus on ionizable and helper lipids, the role of trace PEG-lipids remains underexplored. To address this, we constructed a 45-member PEG-lipid library via Ugi/Passerini reactions, keeping the PEG chain constant at 2 kDa while systematically diversifying the hydrophobic tail and linker structures. High-throughput screening identified Pr-182-BNT (P1B LNP) as a lead candidate. P1B LNPs enable highly efficient and selective mRNA delivery to skeletal muscle while drastically minimizing hepatic off-targeting. This precise tropism originates from enhanced muscle cell uptake and optimized membrane interactions, driven by the lipid's unique branched, asymmetric tail. In Ai9 reporter mice, P1B LNPs drive potent muscle-specific gene editing and reduce off-target recombination. As an RSV mRNA vaccine, they elicit robust antigen-specific IgG titers and expands polyfunctional CD8

Indexed as

LipidsMusclesMuscle, SkeletalNanoparticlesPolyethylene GlycolsRNA, MessengerAnimalsHydrophobic and Hydrophilic InteractionsLiposomesMiceLipid NanoparticlesLipidsLiposomesPolyethylene GlycolsRNA, Messengerlipid nanoparticlesmRNA vaccinesmuscle‐targeted deliveryPEG‐lipids optimizationrespiratory syncytial virus

Identifiers

PMID42489054
PMCPMC13580304

What OpenQuestion holds

Textmetadata
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.