Evidence map›Paper›PMID 42867568›Full record

ArticleScience China. Life sciences2026

Optimization of lipid nanoparticles reduces hepatic accumulation and enhances local delivery of mRNA.

Yue Ma, Yaoxian Han, Jiawei Zhou, Yuxin Xiao, Jie Liu, Wenjie Sun, Hui Yang, Guangyu Hu, Shangang Li, Weizhi Ji and 3 more

Abstract read
PubMed Publisher
In one paragraph

Article in Science China. Life sciences, 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

13 authors.

Yue Ma *State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China.
Yaoxian Han *State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China.
Jiawei Zhou *State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China.
Yuxin XiaoState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China.
Jie LiuState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China.
Wenjie SunState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China.
Hui YangState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China.
Guangyu HuState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China.
Shangang LiState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China.
Weizhi JiState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China. wji@lpbr.cn.
Wenting GuoState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China. guowt@lpbr.cn.
Lei ZhangState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China. zhangl@lpbr.cn.
Yongchang ChenState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China. chenyc@lpbr.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lipid nanoparticles (LNPs) have emerged as the most widely used non-viral gene delivery system, particularly for mRNA therapeutics. However, predominant hepatic accumulation and poor local delivery remain major barriers to their broader application. To address this challenge, we employed a design of experiments (DOE) strategy to systematically refine LNP composition and identified an optimized formulation, SM102M. Compared with the parental SM102 formulation, SM102M markedly reduced liver-associated signal after both intramuscular and intravenous administration, while preserving or enhancing local expression after local delivery. Across multiple local administration routes, including intramuscular, intracerebroventricular, and intravitreal injection, SM102M supported localized gene delivery and gene editing with minimal liver-associated signal. Mechanistically, the altered biodistribution of SM102M was associated with reduced apolipoprotein E (ApoE) binding, lower systemic exposure, and diminished lysosomal escape in hepatocytes. SM102M also showed favorable tolerability and maintained local delivery performance under repeated administration. Together, these findings establish DOE as a practical framework for rational LNP engineering and identify a formulation with reduced hepatic reporter expression and improved local delivery performance.

Indexed as

design of experimentshepatic reporter expressionlipid nanoparticleslocal expressionmRNA deliverySM102

Identifiers

PMID42867568

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.