Evidence map›Paper›PMID 41446212›Full record

ArticlebioRxiv : the preprint server for biology2025

Evaluating the effects of aging on biodistribution and gene silencing activity of lipid-siRNA conjugates delivered into cerebrospinal fluid.

Alexander P Ligocki, Alexander G Sorets, Adam M Abdulrahman, Nora Francini, Joshua C Park, Ju Ha Lee, William T Ford, Sarah M Lyons, Emma L Fritsch, Zachary E Lamantia and 3 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. 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

5 · Who and what money

Authors and funding

13 authors.

Alexander P LigockiDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Alexander G SoretsDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
Adam M AbdulrahmanDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
Nora FranciniDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
Joshua C ParkDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Ju Ha LeeDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
William T FordDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Sarah M LyonsDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Emma L FritschVanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA.
Zachary E LamantiaDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
Plamen P ChristovVanderbilt Institute of Chemical Biology, Molecular Design and Synthesis Center, Vanderbilt University, Nashville, TN, USA.
Craig L DuvallDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Ethan S LippmannDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Ben Ho Park · 1995 to 2026
$172.8M
TRAINING PROGRAM IN ENVIRONMENTAL TOXICOLOGYT32ES007028 · NIEHS · VANDERBILT UNIVERSITY · PI F PETER Guengerich, Fiona Edith Harrison · 1985 to 2026
$15.7M
Perivascular fibroblasts, vascular fibrosis, and their contributions to cerebral amyloid angiopathyRF1NS130334 · NINDS · VANDERBILT UNIVERSITY · PI LIPPMANN, ETHAN, SCHRAG, MATTHEW · 2022 to 2025
$3.9M
Vanderbilt Interdisciplinary Training Program in Alzheimer's DiseaseT32AG058524 · NIA · VANDERBILT UNIVERSITY · PI ANGELA L. JEFFERSON · 2018 to 2026
$3.5M
Targeting brain myeloid cells with siRNA-lipid conjugates for treatment of Alzheimer's diseaseR01AG092015 · NIA · VANDERBILT UNIVERSITY · PI Craig Lewis Duvall, Ethan Lippmann · 2025 to 2026
$1.5M
Targeted lipid-siRNA complexes for SPP1-silencing in Alzheimer's DiseaseF30AG094191 · NIA · VANDERBILT UNIVERSITY · PI Adam Abdulrahman · 2025 to 2026
$90k
NCI NIH HHS P30 CA068485NIA NIH HHS F30 AG094191NIA NIH HHS R01 AG092015NIA NIH HHS T32 AG058524NIEHS NIH HHS T32 ES007028NINDS NIH HHS RF1 NS130334
6 · The paper itself

Abstract

Aging is the primary risk factor for chronic neurodegenerative diseases and is associated with alterations to cerebrospinal fluid (CSF) flow and clearance. CSF delivery is currently the most clinically advanced route of administration for oligonucleotide therapeutics, but it remains poorly understood how aging, which is rarely incorporated into clinical trials, impacts biodistribution, gene silencing activity, and potential toxicity of these compounds. Here, we evaluated a lipid-siRNA conjugate (L2-siRNA) for potential age-related changes to CSF-mediated delivery, mRNA silencing, and safety. We found that L2-siRNA exhibited comparable biodistribution and on-target silencing of Huntingtin (

Identifiers

PMID41446212
PMCPMC12724171

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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.