Evidence map›Paper›PMID 37620930›Full record

ArticleFluids and barriers of the CNS2023

Enhanced in vivo blood brain barrier transcytosis of macromolecular cargo using an engineered pH-sensitive mouse transferrin receptor binding nanobody.

Thomas J Esparza, Shiran Su, Caroline M Francescutti, Elvira Rodionova, Joong Hee Kim, David L Brody

Open access · goldAbstract read
In one paragraph

Article in Fluids and barriers of the CNS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

21 citing papers in PubMed, 36 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Thomas J EsparzaNational Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.
Shiran SuNational Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.
Caroline M FrancescuttiNational Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.
Elvira RodionovaNational Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.
Joong Hee KimNational Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.
David L BrodyNational Institute of Neurological Disorders and Stroke, Bethesda, MD, USA. david.brody@nih.gov.
National Institute of Neurological Disorders and Stroke · USUniformed Services University of the Health Sciences · USWashington University in St. Louis · US

Funding

Development of Brain MRI Contrast AgentsZIANS003170 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI KORETSKY, ALAN · 2019 to 2024
$7.7M
6 · The paper itself

Abstract

backgroundThe blood brain barrier limits entry of macromolecular diagnostic and therapeutic cargos. Blood brain barrier transcytosis via receptor mediated transport systems, such as the transferrin receptor, can be used to carry macromolecular cargos with variable efficiency. Transcytosis involves trafficking through acidified intracellular vesicles, but it is not known whether pH-dependent unbinding of transport shuttles can be used to improve blood brain barrier transport efficiency.

methodsA mouse transferrin receptor binding nanobody, NIH-mTfR-M1, was engineered to confer greater unbinding at pH 5.5 vs 7.4 by introducing multiple histidine mutations. The histidine mutant nanobodies were coupled to neurotensin for in vivo functional blood brain barrier transcytosis testing via central neurotensin-mediated hypothermia in wild-type mice. Multi-nanobody constructs including the mutant M1

resultsThe most effective histidine mutant, M1

conclusionThe pH-sensitive mouse transferrin receptor binding nanobody M1

Indexed as

Blood-Brain BarrierHypothermiaAnimalsHistidineHydrogen-Ion ConcentrationMiceNeurotensinTranscytosisHistidineNeurotensinBlood brain barrierCapillary depletionHistidineMouseNanobodyNeurotensinP2X7 receptorTransferrin receptor

Identifiers

PMID37620930
PMCPMC10463325
OpenAlexW4386142084

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.