Evidence map›Paper›PMID 29200285›Full record

ArticleBioconjugate chemistry2018

Site-Specific Modification of Single-Chain Antibody Fragments for Bioconjugation and Vascular Immunotargeting.

Colin F Greineder, Carlos H Villa, Landis R Walsh, Raisa Y Kiseleva, Elizabeth D Hood, Makan Khoshnejad, Robert Warden-Rothman, Andrew Tsourkas, Vladimir R Muzykantov

Abstract read
In one paragraph

Article in Bioconjugate chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

16 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. Affinity targeting of therapeutic proteins to the bone surface-local delivery of sclerostin-neutralizing antibody enhances efficacy.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024
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  7. Review
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  11. Bivalent engagement of endothelial surface antigens is critical to prolonged surface targeting and protein delivery in vivo.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
    Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. High-throughput in vivo screen of functional mRNA delivery identifies nanoparticles for endothelial cell gene editing.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
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 1 institution in 1 country.

Colin F GreinederDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine and ‡Department of Bioengineering, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.ORCID 0000-0001-9740-7672
Carlos H VillaDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine and ‡Department of Bioengineering, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
Landis R WalshDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine and ‡Department of Bioengineering, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
Raisa Y KiselevaDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine and ‡Department of Bioengineering, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
Elizabeth D HoodDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine and ‡Department of Bioengineering, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
Makan KhoshnejadDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine and ‡Department of Bioengineering, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.ORCID 0000-0001-5143-304X
Robert Warden-RothmanDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine and ‡Department of Bioengineering, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
Andrew TsourkasDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine and ‡Department of Bioengineering, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.ORCID 0000-0001-7758-1753
Vladimir R MuzykantovDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine and ‡Department of Bioengineering, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
Translational Therapeutics (United States) · US

Funding

HEMATOLOGY CLINICAL RESEARCH TRAINING PROGRAMT32HL007439 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI LAWRENCE F BRASS, PETER S KLEIN · 1985 to 2026
$17.1M
TRAINING GRANT IN HEMOSTASIS AND THROMBOSIST32HL007971 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI Rodney M Camire · 2001 to 2026
$10.6M
TRANSFUSION MEDICINE RESEARCH TRAINING PROGRAMT32HL007775 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI SIEGEL, DONALD LAWRENCE · 1993 to 2023
$2.8M
Targeting novel biotherapeutics to endotheliumR01HL128398 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R · 2015 to 2018
$2.2M
Endothelial targeting of antioxidantsR01HL126874 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R · 2016 to 2019
$1.7M
ICAM-1 targeted thrombomodulin: an experimental therapeutic for the Acute Respiratory Distress SyndromeK08HL130430 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI GREINEDER, COLIN FRED · 2016 to 2020
$665k
Bioconjugate technique for site-specific attachment of IgG onto nanoparticlesR21EB018863 · NIBIB · UNIVERSITY OF PENNSYLVANIA · PI TSOURKAS, ANDREW · 2014 to 2015
$440k
A facile method for producing bispecific antibodies from full-length IgGR21CA187657 · NCI · UNIVERSITY OF PENNSYLVANIA · PI TSOURKAS, ANDREW · 2014 to 2015
$383k
NCI NIH HHS R21 CA187657NHLBI NIH HHS K08 HL130430NHLBI NIH HHS R01 HL126874NHLBI NIH HHS R01 HL128398NHLBI NIH HHS T32 HL007439NHLBI NIH HHS T32 HL007775NHLBI NIH HHS T32 HL007971NIBIB NIH HHS R21 EB018863
6 · The paper itself

Abstract

The conjugation of antibodies to drugs and drug carriers improves delivery to target tissues. Widespread implementation and effective translation of this pharmacologic strategy awaits the development of affinity ligands capable of a defined degree of modification and highly efficient bioconjugation without loss of affinity. To date, such ligands are lacking for the targeting of therapeutics to vascular endothelial cells. To enable site-specific, click-chemistry conjugation to therapeutic cargo, we used the bacterial transpeptidase, sortase A, to attach short azidolysine containing peptides to three endothelial-specific single chain antibody fragments (scFv). While direct fusion of a recognition motif (sortag) to the scFv C-terminus generally resulted in low levels of sortase-mediated modification, improved reaction efficiency was observed for one protein, in which two amino acids had been introduced during cloning. This prompted insertion of a short, semi-rigid linker between scFv and sortag. The linker significantly enhanced modification of all three proteins, to the extent that unmodified scFv could no longer be detected. As proof of principle, purified, azide-modified scFv was conjugated to the antioxidant enzyme, catalase, resulting in robust endothelial targeting of functional cargo in vitro and in vivo.

Indexed as

Amino Acid SequenceAminoacyltransferasesAnimalsBacterial ProteinsCatalaseCell LineClick ChemistryCysteine EndopeptidasesHumansIntercellular Adhesion Molecule-1MiceMice, Inbred C57BLModels, MolecularPlatelet Endothelial Cell Adhesion Molecule-1Single-Chain AntibodiesTissue DistributionAminoacyltransferasesBacterial ProteinsCatalaseCysteine EndopeptidasesIntercellular Adhesion Molecule-1Platelet Endothelial Cell Adhesion Molecule-1Single-Chain Antibodiessortase A

Identifiers

PMID29200285
PMCPMC6477694
OpenAlexW2772307571

What OpenQuestion holds

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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.