Evidence map›Paper›PMID 26855052›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2016

Molecular engineering of high affinity single-chain antibody fragment for endothelial targeting of proteins and nanocarriers in rodents and humans.

Colin F Greineder, Elizabeth D Hood, Anning Yao, Makan Khoshnejad, Jake S Brenner, Ian H Johnston, Mortimer Poncz, Claudia Gottstein, Vladimir R Muzykantov

Abstract read
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

13 citing papers in PubMed, 27 citations in OpenAlex.

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  8. Targeting therapeutics to endothelium: are we there yet?Drug delivery and translational research · 2018
    Review
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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

9 authors at 5 institutions in 1 country.

Colin F GreinederDepartment of Pharmacology, Institute for Translational Medicine and Therapeutics, 3400 Civic Center Blvd, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Center for Targeted Therapeutics and Translational Nanomedicine, Institute for Translational Medicine and Therapeutics, 3400 Civic Center Blvd, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States. Electronic address: cgreineder@gmail.com.
Elizabeth D HoodDepartment of Pharmacology, Institute for Translational Medicine and Therapeutics, 3400 Civic Center Blvd, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Center for Targeted Therapeutics and Translational Nanomedicine, Institute for Translational Medicine and Therapeutics, 3400 Civic Center Blvd, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
Anning YaoDepartment of Pharmacology, Institute for Translational Medicine and Therapeutics, 3400 Civic Center Blvd, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Center for Targeted Therapeutics and Translational Nanomedicine, Institute for Translational Medicine and Therapeutics, 3400 Civic Center Blvd, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
Makan KhoshnejadDepartment of Pharmacology, Institute for Translational Medicine and Therapeutics, 3400 Civic Center Blvd, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Center for Targeted Therapeutics and Translational Nanomedicine, Institute for Translational Medicine and Therapeutics, 3400 Civic Center Blvd, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
Jake S BrennerDepartment of Pharmacology, Institute for Translational Medicine and Therapeutics, 3400 Civic Center Blvd, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Center for Targeted Therapeutics and Translational Nanomedicine, Institute for Translational Medicine and Therapeutics, 3400 Civic Center Blvd, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
Ian H JohnstonDepartment of Pediatrics, Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States.
Mortimer PonczDepartment of Pediatrics, Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States.
Claudia GottsteinDepartment of Molecular, Cellular and Developmental Biology, University of California Santa Barbara, Santa Barbara, CA 93106, United States.
Vladimir R MuzykantovDepartment of Pharmacology, Institute for Translational Medicine and Therapeutics, 3400 Civic Center Blvd, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Center for Targeted Therapeutics and Translational Nanomedicine, Institute for Translational Medicine and Therapeutics, 3400 Civic Center Blvd, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
Translational Therapeutics (United States) · USChildren's Hospital of Philadelphia · USTarget (United States) · USUniversity of California, Santa Barbara · USUniversity of Pennsylvania · US

Funding

HEMATOLOGY CLINICAL RESEARCH TRAINING PROGRAMT32HL007439 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI LAWRENCE F BRASS, PETER S KLEIN · 1985 to 2026
$17.1M
Multidisciplinary Training in Cardiovascular BiologyT32HL007954 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DAVIES, PETER FRANCIS · 2000 to 2019
$9.9M
Targeted nanomedicine for ALI and I/RR01HL125462 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R · 2015 to 2018
$2.3M
Targeting novel biotherapeutics to endotheliumR01HL128398 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R · 2015 to 2018
$2.2M
Targeted delivery of thrombomodulin in lung diseaseR01HL091950 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R · 2009 to 2013
$1.9M
Targeting of Drugs to ICAMR01HL071175 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R · 2002 to 2005
$1.4M
NHLBI NIH HHS R01 HL071175NHLBI NIH HHS R01 HL091950NHLBI NIH HHS R01-HL091950NHLBI NIH HHS R01 HL125462NHLBI NIH HHS R01 HL128398NHLBI NIH HHS R01-HL128398NHLBI NIH HHS T32 HL007439NHLBI NIH HHS T32 HL007954
6 · The paper itself

Abstract

Endothelial cells (EC) represent an important target for pharmacologic intervention, given their central role in a wide variety of human pathophysiologic processes. Studies in lab animal species have established that conjugation of drugs and carriers with antibodies directed to surface targets like the Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1, a highly expressed endothelial transmembrane protein) help to achieve specific therapeutic interventions in ECs. To translate such "vascular immunotargeting" to clinical practice, it is necessary to replace antibodies by advanced ligands that are more amenable to use in humans. We report the molecular design of a single chain variable antibody fragment (scFv) that binds with high affinity to human PECAM-1 and cross-reacts with its counterpart in rats and other animal species, allowing parallel testing in vivo and in human endothelial cells in microfluidic model. Site-specific modification of the scFv allows conjugation of protein cargo and liposomes, enabling their endothelial targeting in these models. This study provides a template for molecular engineering of ligands, enabling studies of drug targeting in animal species and subsequent use in humans.

Indexed as

Drug Delivery SystemsAmino Acid SequenceAnimalsAntibody AffinityCell LineEndothelial CellsEndotheliumHumansHuman Umbilical Vein Endothelial CellsLiposomesPlatelet Endothelial Cell Adhesion Molecule-1RatsSingle-Chain AntibodiesLiposomesPlatelet Endothelial Cell Adhesion Molecule-1Single-Chain AntibodiesEndothelial drug deliveryImmunotargetingPECAM-1Single chain variable fragment

Identifiers

PMID26855052
PMCPMC4964279
OpenAlexW2257165808

What OpenQuestion holds

Textmetadata
LicenceTDM
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.