Evidence map›Paper›PMID 29947573›Full record

ArticlemAbs2018

Extending human IgG half-life using structure-guided design.

Brian J Booth, Boopathy Ramakrishnan, Kristin Narayan, Andrew M Wollacott, Gregory J Babcock, Zachary Shriver, Karthik Viswanathan

Open access · goldAbstract read
In one paragraph

Article in mAbs, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed
5.4field-weighted citation impact, top 4% 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

83 citing papers in PubMed, 109 citations in OpenAlex.

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  13. A multivalent nanobody-drug conjugate to prevent and treat influenza virus infections.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  18. An engineered antibody-lectin conjugate targeting the HIV glycan shield protects humanized mice against HIV challenge.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
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23 more citing papers are in PubMed but not listed here.

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

7 authors at 1 institution in 1 country.

Brian J Bootha Visterra, Inc., Waltham , MA , USA.ORCID 0000-0001-9677-338X
Boopathy Ramakrishnana Visterra, Inc., Waltham , MA , USA.
Kristin Narayana Visterra, Inc., Waltham , MA , USA.
Andrew M Wollacotta Visterra, Inc., Waltham , MA , USA.ORCID 0000-0001-9848-8742
Gregory J Babcocka Visterra, Inc., Waltham , MA , USA.
Zachary Shrivera Visterra, Inc., Waltham , MA , USA.
Karthik Viswanathana Visterra, Inc., Waltham , MA , USA.ORCID 0000-0002-1288-9965
Visterra (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Engineering of antibodies for improved pharmacokinetics through enhanced binding to the neonatal Fc receptor (FcRn) has been demonstrated in transgenic mice, non-human primates and humans. Traditionally, such approaches have largely relied on random mutagenesis and display formats, which fail to address related critical attributes of the antibody, such as effector functions or biophysical stability. We have developed a structure- and network-based framework to interrogate the engagement of IgG with multiple Fc receptors (FcRn, C1q, TRIM21, FcγRI, FcγRIIa/b, FcγRIIIa) simultaneously. Using this framework, we identified features that govern Fc-FcRn interactions and identified multiple distinct pathways for enhancing FcRn binding in a pH-specific manner. Network analysis provided a novel lens to study the allosteric impact of half-life-enhancing Fc mutations on FcγR engagement, which occurs distal to the FcRn binding site. Applying these principles, we engineered a panel of unique Fc variants that enhance FcRn binding while maintaining robust biophysical properties and wild type-like binding to activating receptors. An antibody harboring representative Fc designs demonstrates a half-life improvement of > 9 fold in transgenic mice and > 3.5 fold in cynomolgus monkeys, and maintains robust effector functions such as antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity.

Indexed as

Allosteric RegulationAnimalsAntibody AffinityAntibody-Dependent Cell CytotoxicityB-LymphocytesCell LineGene Regulatory NetworksHalf-LifeHumansImmunoglobulin GMacaca fascicularisMiceMice, TransgenicMutationProtein BindingProtein EngineeringImmunoglobulin GReceptors, Fcamino acid interaction networkAntibodyeffector functionsFcRnhalf-lifeneonatal Fc receptorpharmacokineticsstructure-guided engineering

Identifiers

PMID29947573
PMCPMC6204840
OpenAlexW2811304917

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.