Evidence map›Paper›PMID 39962245›Full record

ArticleNature materials2025

Blood-brain-barrier-crossing lipid nanoparticles for mRNA delivery to the central nervous system.

Chang Wang, Yonger Xue, Tamara Markovic, Haoyuan Li, Siyu Wang, Yichen Zhong, Shi Du, Yuebao Zhang, Xucheng Hou, Yang Yu and 19 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature materials, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.

0numbers the graph read from it
0cells of the map it votes in
88citing 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

88 citing papers in PubMed.

  1. Article
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  7. Bioactive lipid-derived nanoparticles for RNA delivery.Materials today (Kidlington, England) · 2026
    Article
  8. Article
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  18. Article
  19. Single-ligand dual-targeting lipid nanoparticles for therapeutic mRNA delivery to glioblastoma across the blood-brain barrier.Journal of controlled release : official journal of the Controlled Release Society · 2026
    Article
  20. Targeting mNature communications · 2026
    Article

28 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

29 authors.

Chang Wang *Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Biomedical Engineering and Imaging Institute, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0009-0005-1630-9453
Yonger Xue *Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Biomedical Engineering and Imaging Institute, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-6022-2487
Tamara Markovic *Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Haoyuan LiIcahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Biomedical Engineering and Imaging Institute, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Siyu WangIcahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Biomedical Engineering and Imaging Institute, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Yichen ZhongIcahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Biomedical Engineering and Imaging Institute, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0003-3652-1257
Shi DuIcahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Biomedical Engineering and Imaging Institute, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Yuebao ZhangDivision of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA.ORCID 0009-0000-7883-1937
Xucheng HouIcahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Biomedical Engineering and Imaging Institute, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0001-7833-8704
Yang YuDivision of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA.ORCID 0000-0001-6885-019X
Zhengwei LiuIcahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Biomedical Engineering and Imaging Institute, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0009-0003-5105-6709
Meng TianIcahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Biomedical Engineering and Imaging Institute, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0001-7719-9896
Diana D KangIcahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Biomedical Engineering and Imaging Institute, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Leiming WangIcahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Biomedical Engineering and Imaging Institute, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Kaiyuan GuoIcahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Biomedical Engineering and Imaging Institute, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0009-0001-0621-9543
Dinglingge CaoIcahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Biomedical Engineering and Imaging Institute, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Jingyue YanIcahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Biomedical Engineering and Imaging Institute, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Binbin DengCenter for Electron Microscopy and Analysis, The Ohio State University, Columbus, OH, USA.
David W McCombCenter for Electron Microscopy and Analysis, The Ohio State University, Columbus, OH, USA.ORCID 0000-0003-3763-9652
Ramon E ParsonsDepartment of Oncological Sciences, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Angelica M Minier-ToribioNash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-8860-5973
Leanne M HoltNash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Jiayi PanBiogen, Cambridge, MA, USA.
Alice HashemiCharles Bronfman Institute for Personalized Medicine, Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Brian H KopellCharles Bronfman Institute for Personalized Medicine, Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-6955-4787
Alexander W CharneyCharles Bronfman Institute for Personalized Medicine, Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0001-8135-6858
Eric J NestlerNash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. eric.nestler@mssm.edu.ORCID 0000-0002-7905-2000
Paul C PengBiogen, Cambridge, MA, USA. paul.peng@biogen.com.ORCID 0009-0006-7801-4738
Yizhou DongIcahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Biomedical Engineering and Imaging Institute, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. yizhou.dong@mssm.edu.ORCID 0000-0001-5786-0659

Funding

Transcription Factors in Stimulant and Opioid ActionP01DA047233 · NIDA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Anne Schaefer · 2019 to 2026
$16.5M
RESEARCH TRAINING - BIOLOGICAL SCIENCEST32MH014276 · NIMH · YALE UNIVERSITY · PI Marina R Picciotto · 1985 to 2026
$7.2M
Small molecule modulators of ΔFosB FunctionR01DA040621 · NIDA · UNIVERSITY OF TEXAS MED BR GALVESTON · PI NESTLER, ERIC J., ROBISON, ALFRED J · 2016 to 2025
$7.1M
Training Program in Substance Use DisordersT32DA053558 · NIDA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Paul J. Kenny · 2021 to 2026
$2.6M
Construction of in vivo mRNA delivery systemsR35GM144117 · NIGMS · OHIO STATE UNIVERSITY · PI Yizhou Dong · 2022 to 2026
$2.4M
NIDA NIH HHS P01 DA047233NIDA NIH HHS R01 DA040621NIDA NIH HHS T32 DA053558NIGMS NIH HHS R35 GM144117NIMH NIH HHS T32 MH014276U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM144117U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) P01DA047233
6 · The paper itself

Abstract

The systemic delivery of mRNA molecules to the central nervous system is challenging as they need to cross the blood-brain barrier (BBB) to reach into the brain. Here we design and synthesize 72 BBB-crossing lipids fabricated by conjugating BBB-crossing modules and amino lipids, and use them to assemble BBB-crossing lipid nanoparticles for mRNA delivery. Screening and structure optimization studies resulted in a lead formulation that has substantially higher mRNA delivery efficiency into the brain than those exhibited by FDA-approved lipid nanoparticles. Studies in distinct mouse models show that these BBB-crossing lipid nanoparticles can transfect neurons and astrocytes of the whole brain after intravenous injections, being well tolerated across several dosage regimens. Moreover, these nanoparticles can deliver mRNA to human brain ex vivo samples. Overall, these BBB-crossing lipid nanoparticles deliver mRNA to neurons and astrocytes in broad brain regions, thereby being a promising platform to treat a range of central nervous system diseases.

Indexed as

Blood-Brain BarrierCentral Nervous SystemRNA, MessengerAnimalsHumansLipidsLiposomesMiceNanoparticlesNeuronsLipid NanoparticlesLipidsLiposomesRNA, Messenger

Identifiers

PMID39962245
PMCPMC12514551

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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.