Evidence map›Paper›PMID 29379029›Full record

ArticleScientific reports2018

Molecular engineering of antibodies for site-specific covalent conjugation using CRISPR/Cas9.

Makan Khoshnejad, Jacob S Brenner, William Motley, Hamideh Parhiz, Colin F Greineder, Carlos H Villa, Oscar A Marcos-Contreras, Andrew Tsourkas, Vladimir R Muzykantov

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

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

14 citing papers in PubMed, 36 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Research Progress on Cell Membrane-Coated Biomimetic Delivery Systems.Frontiers in bioengineering and biotechnology · 2021
    Review
  9. 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
  10. Advances in simultaneous PET/MR for imaging neuroreceptor function.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020
    Review
  11. Article
  12. Engineering Cell Membrane-Based Nanotherapeutics to Target Inflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2019
    Review
  13. Article
  14. 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 2 institutions in 1 country.

Makan KhoshnejadDepartment of Pharmacology, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. makank@mail.med.upenn.edu.
Jacob S BrennerDepartment of Pharmacology, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. jake.brenner@gmail.com.
William MotleyDepartment of Neurology, Johns Hopkins University, Baltimore, MD, USA.
Hamideh ParhizDepartment of Pharmacology, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Colin F GreinederDepartment of Pharmacology, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Carlos H VillaDepartment of Pharmacology, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Oscar A Marcos-ContrerasDepartment of Pharmacology, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Andrew TsourkasDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-7758-1753
Vladimir R MuzykantovDepartment of Pharmacology, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. muzykant@mail.med.upenn.edu.
University of Pennsylvania · USJohns Hopkins University · US

Funding

Multidisciplinary Training in Cardiovascular BiologyT32HL007954 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DAVIES, PETER FRANCIS · 2000 to 2019
$9.9M
TRANSFUSION MEDICINE RESEARCH TRAINING PROGRAMT32HL007775 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI SIEGEL, DONALD LAWRENCE · 1993 to 2023
$2.8M
Targeted nanomedicine for ALI and I/RR01HL125462 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R · 2015 to 2018
$2.3M
Endothelial targeting of antioxidantsR01HL126874 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R · 2016 to 2019
$1.7M
Nanonscale drug carriers for the treatment of acute respiratory distress syndromeK08HL138269 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI BRENNER, JACOB · 2017 to 2021
$746k
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
NHLBI NIH HHS K08 HL130430NHLBI NIH HHS K08 HL138269NHLBI NIH HHS R01 HL125462NHLBI NIH HHS R01 HL126874NHLBI NIH HHS T32 HL007775NHLBI NIH HHS T32 HL007954
6 · The paper itself

Abstract

Site-specific modification of antibodies has become a critical aspect in the development of next-generation immunoconjugates meeting criteria of clinically acceptable homogeneity, reproducibility, efficacy, ease of manufacturability, and cost-effectiveness. Using CRISPR/Cas9 genomic editing, we developed a simple and novel approach to produce site-specifically modified antibodies. A sortase tag was genetically incorporated into the C-terminal end of the third immunoglobulin heavy chain constant region (CH3) within a hybridoma cell line to manufacture antibodies capable of site-specific conjugation. This enabled an effective enzymatic site-controlled conjugation of fluorescent and radioactive cargoes to a genetically tagged mAb without impairment of antigen binding activity. After injection in mice, these immunoconjugates showed almost doubled specific targeting in the lung vs. chemically conjugated maternal mAb, and concomitant reduction in uptake in the liver and spleen. The approach outlined in this work provides a facile method for the development of more homogeneous, reproducible, effective, and scalable antibody conjugates for use as therapeutic and diagnostic tools.

Indexed as

AnimalsAntibodies, MonoclonalAntigensCell Line, TumorClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsCysteineHumansImmunoconjugatesMiceRatsReproducibility of ResultsAntibodies, MonoclonalAntigensCysteineImmunoconjugates

Identifiers

PMID29379029
PMCPMC5789018
OpenAlexW2803920758

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.