Evidence map›Paper›PMID 31106264›Full record

ArticleScience advances2019

Identification of variable lymphocyte receptors that can target therapeutics to pathologically exposed brain extracellular matrix.

Benjamin J Umlauf, Paul A Clark, Jason M Lajoie, Julia V Georgieva, Samantha Bremner, Brantley R Herrin, John S Kuo, Eric V Shusta

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.5field-weighted citation impact, top 17% of its field
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

19 citing papers in PubMed, 29 citations in OpenAlex.

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  12. Development of Novel Therapeutics Targeting the Blood-Brain Barrier: From Barrier to Carrier.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021
    Review
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  16. Antibody screening using a human iPSC-based blood-brain barrier model identifies antibodies that accumulate in the CNS.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
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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

8 authors at 2 institutions in 1 country.

Benjamin J UmlaufDepartment of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, USA.ORCID 0000-0002-1882-6092
Paul A ClarkDepartment of Neurological Surgery, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.ORCID 0000-0002-1608-1146
Jason M LajoieDepartment of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, USA.
Julia V GeorgievaDepartment of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, USA.
Samantha BremnerDepartment of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, USA.ORCID 0000-0003-3465-0442
Brantley R HerrinEmory University, Atlanta, GA, USA.ORCID 0000-0002-1842-6806
John S KuoDepartment of Neurological Surgery, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.ORCID 0000-0001-6809-4806
Eric V ShustaDepartment of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, USA.ORCID 0000-0002-4297-0158
University of Wisconsin–Madison · USEmory University · US

Funding

BIOTECHNOLOGY TRAINING PROGRAMT32GM008349 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI FOX, BRIAN G · 1989 to 2019
$22.5M
Identification of Lamprey Antibodies Capable of Noninvasive Brain Drug DeliveryR01NS099158 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI SHUSTA, ERIC V · 2017 to 2021
$1.7M
Using lamprey antibodies to profile the blood-brain barrierR21NS091851 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI SHUSTA, ERIC V · 2015 to 2016
$430k
NIGMS NIH HHS T32 GM008349NINDS NIH HHS R01 NS099158NINDS NIH HHS R21 NS091851
6 · The paper itself

Abstract

Diseases that lead to blood-brain barrier (BBB) disruption will pathologically expose normally inaccessible brain extracellular matrix (ECM) to circulating blood components. Therefore, we hypothesized that brain ECM-targeting moieties could specifically target the disrupted BBB and potentially deliver therapies. Variable lymphocyte receptors (VLRs) that preferentially associate with brain ECM were identified from an immune VLR library via yeast surface display biopanning coupled with a moderate throughput ECM screen. Brain ECM binding of VLR clones to murine and human brain tissue sections was confirmed. After systemic administration, P1C10, the lead brain ECM-targeting VLR candidate, specifically accumulated in brains with mannitol-disrupted BBB and at disrupted BBB regions in two different intracranial glioblastoma models. We also demonstrate P1C10's ability to deliver doxorubicin-loaded liposomes, leading to significantly improved survival in glioblastoma-bearing mice. Thus, VLRs can be used to selectively target pathologically exposed brain ECM and deliver drug payloads.

Indexed as

3T3 CellsAnimalsBlood-Brain BarrierBrainBrain NeoplasmsCell Line, TumorDoxorubicinExtracellular MatrixGlioblastomaHumansKaplan-Meier EstimateKineticsLiposomesLymphocytesMannitolMiceDoxorubicinLiposomesMannitol

Identifiers

PMID31106264
PMCPMC6520025
OpenAlexW2945472292

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.