Evidence map›Paper›PMID 40945532›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2025

Intravenous lipid-siRNA conjugate mediates gene silencing at the blood-brain barrier and blood-CSF barrier.

Alexander G Sorets, Katrina R Schwensen, Nora Francini, Andrew Kjar, Sarah Lyons, Joshua C Park, Dillon Palmer, Adam M Abdulrahman, Rebecca P Cowell, Ketaki A Katdare and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Alexander G SoretsDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
Katrina R SchwensenDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Nora FranciniDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
Andrew KjarDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
Sarah LyonsDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Joshua C ParkDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Dillon PalmerDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Adam M AbdulrahmanDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
Rebecca P CowellDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Ketaki A KatdareVanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA.
Ella N HoogenboezemDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
Angela WangCell and Developmental Biology, Vanderbilt University, Nashville, TN, USA.
Alexander P LigockiDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Rebecca J EmbalabalaVanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA.
Neil DaniCell and Developmental Biology, Vanderbilt University, Nashville, TN, USA.
Craig L DuvallDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA; Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA. Electronic address: craig.duvall@vanderbilt.edu.
Ethan S LippmannDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA; Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA; Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: ethan.s.lippmann@vanderbilt.edu.

Funding

Overall: Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Center at VanderbiltP50HD103537 · NICHD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Jeffrey L Neul · 2020 to 2026
$10.3M
Albumin hitchhiking siRNAs for gene targeting in aged brainR21AG077807 · NIA · VANDERBILT UNIVERSITY · PI DUVALL, CRAIG LEWIS, LIPPMANN, ETHAN · 2022 to 2023
$420k
NIA NIH HHS R21 AG077807NICHD NIH HHS P50 HD103537
6 · The paper itself

Abstract

Barriers of the central nervous system (CNS), such as the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB), regulate the two-way exchange of material between the blood and CNS. While the BBB and BCSFB can become dysfunctional in patients with chronic CNS diseases, few studies have focused on strategies for targeting these interfaces. Here, we showed that an intravenously administered lipid-siRNA conjugate was delivered to and silenced genes within brain endothelial cells and choroid plexus epithelial cells, which comprise the BBB and BCSFB, respectively. A single intravenous dose of lipid-siRNA conjugate was delivered to ∼100 % of brain endothelial cells and major choroid plexus cell types, without substantial delivery into brain parenchymal tissue. Sustained mRNA and protein silencing was achieved in both brain endothelial cells and bulk choroid plexus tissues. Moreover, single cell RNA sequencing demonstrated gene knockdown in capillaries, venous endothelial cells, and choroid plexus epithelial cells without silencing genes in parenchymal cell populations. Collectively, this work establishes an effective nonviral framework to mediate gene inhibition in the brain barriers.

Indexed as

Blood-Brain BarrierGene SilencingLipidsRNA, Small InterferingAnimalsBrainChoroid PlexusEndothelial CellsEpithelial CellsHumansMaleMiceMice, Inbred C57BLLipidsRNA, Small InterferingBlood-brain barrierChoroid plexusGene therapysiRNA

Identifiers

PMID40945532
PMCPMC13191969

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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.