Evidence map›Paper›PMID 42359610›Full record

ArticleSmall methods2026

Spatial Tail Design in Ionizable Lipids Enhances the Safety and Efficacy of mRNA Delivery.

Haiyang Li, Chongyu Tian, Weining Kong, Jonathan Weiss, Jiahan Gang, Taorui Zhong, Yuanwu Ma, Jiangsheng Xu, Wanbo Tai, Fang Zeng and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Small methods, 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

11 authors.

Haiyang LiBiomedical Division, State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, School of Materials Science and Engineering, South China University of Technology, Guangzhou, China.
Chongyu TianInstitute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, China.
Weining KongInstitute of Laboratory Animal Science, Peking Union Medicine College, Chinese Academy of Medical Sciences, Beijing, China.
Jonathan WeissGeneral Therapeutics, Inc., Gaithersburg, Maryland, USA.
Jiahan GangInstitute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, China.
Taorui ZhongBiomedical Division, State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, School of Materials Science and Engineering, South China University of Technology, Guangzhou, China.
Yuanwu MaInstitute of Laboratory Animal Science, Peking Union Medicine College, Chinese Academy of Medical Sciences, Beijing, China.
Jiangsheng XuGeneral Therapeutics, Inc., Gaithersburg, Maryland, USA.ORCID https://orcid.org/0000-0002-9595-9550
Wanbo TaiInstitute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, China.
Fang ZengBiomedical Division, State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, School of Materials Science and Engineering, South China University of Technology, Guangzhou, China.ORCID https://orcid.org/0000-0002-6607-3494
Shuizhu WuBiomedical Division, State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, School of Materials Science and Engineering, South China University of Technology, Guangzhou, China.ORCID https://orcid.org/0000-0002-6739-0694

Funding

NSFC 22274057NSFC 52373209NSFC 82271872NSFC 82341046
6 · The paper itself

Abstract

Messenger RNA (mRNA) delivery critically depends on the molecular architecture of ionizable lipids within lipid nanoparticles (LNPs). We report a modular platform of sterol-containing ionizable lipids designed to probe how sterol motifs and branched dialkyl tails govern in vivo performance. Each lipid incorporates a sterol-derived (e.g., cholesterol) tail and a dialkyl tail with tunable branching and spatial arrangement, enabling systematic control over packing behavior, protonation characteristics, and nanoparticle assembly. The resulting LNPs exhibited favorable apparent pKa values (6.2-6.8), encapsulation efficiencies higher than 90%, and strong transfection potency. Our lead LNP (L1-aCho-e3 LNP) exhibited higher transfection efficiency than the benchmark SM-102 LNP. Incorporation of cationic (DOTAP) or anionic (DOPA) lipids as fifth components further demonstrated reorienting biodistribution from liver to lung or spleen. Finally, mRNA

Indexed as

LipidsRNA, MessengerAnimalsMiceNanoparticlesSterolsTissue DistributionTransfectionLipidsRNA, MessengerSterolsionizable lipidslipid nanoparticlesmRNAmRNA therapeuticsRNA delivery

Identifiers

PMID42359610
PMCPMC13397292

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.