Evidence map›Paper›PMID 40319060›Full record

ArticleNature communications2025

Leveraging neonatal Fc receptor (FcRn) to enhance antibody transport across the blood brain barrier.

Julien Lafrance-Vanasse, Shraddha S Sadekar, Yanli Yang, Daniela Bumbaca Yadav, William J Meilandt, Monica K Wetzel-Smith, Hao Cai, Susan R Crowell, Van Nguyen, Vivian Lee and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

6 citing papers in PubMed.

  1. 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

19 authors.

Julien Lafrance-Vanasse *Department of Protein Chemistry, Genentech, Inc., South San Francisco, CA, 94080, USA.ORCID http://orcid.org/0000-0001-8807-6277
Shraddha S Sadekar *Department of Translational Pharmacokinetics and Pharmacodynamics, Genentech, Inc., South San Francisco, CA, 94080, USA.
Yanli Yang *Department of Antibody Engineering, Genentech, Inc., South San Francisco, CA, 94080, USA.
Daniela Bumbaca YadavDepartment of Translational Pharmacokinetics and Pharmacodynamics, Genentech, Inc., South San Francisco, CA, 94080, USA.
William J MeilandtDepartment of Neuroscience, Genentech, Inc., South San Francisco, CA, 94080, USA.
Monica K Wetzel-SmithDepartment of Neuroscience, Genentech, Inc., South San Francisco, CA, 94080, USA.
Hao CaiDepartment of Translational Pharmacokinetics and Pharmacodynamics, Genentech, Inc., South San Francisco, CA, 94080, USA.
Susan R CrowellDepartment of Translational Pharmacokinetics and Pharmacodynamics, Genentech, Inc., South San Francisco, CA, 94080, USA.
Van NguyenDepartment of Bioanalytical Science, Genentech, Inc., South San Francisco, CA, 94080, USA.
Vivian LeeDepartment of Antibody Engineering, Genentech, Inc., South San Francisco, CA, 94080, USA.
Ben ChihDepartment of Biochemical and Cellular Pharmacology, Genentech, Inc., South San Francisco, CA, 94080, USA.ORCID http://orcid.org/0000-0002-1248-8379
Mandy KwongDepartment of Biochemical and Cellular Pharmacology, Genentech, Inc., South San Francisco, CA, 94080, USA.
Pamela ChanDepartment of Biochemical and Cellular Pharmacology, Genentech, Inc., South San Francisco, CA, 94080, USA.
Sara SantagostinoDepartment of Translational Safety, Genentech, Inc., South San Francisco, CA, 94080, USA.
Donna LeeDepartment of Translational Safety, Genentech, Inc., South San Francisco, CA, 94080, USA.ORCID http://orcid.org/0000-0003-1061-1385
Shan ChungDepartment of Bioanalytical Science, Genentech, Inc., South San Francisco, CA, 94080, USA.ORCID http://orcid.org/0000-0002-5494-2103
Greg A LazarDepartment of Antibody Engineering, Genentech, Inc., South San Francisco, CA, 94080, USA.ORCID http://orcid.org/0000-0003-2169-8703
James A ErnstDepartment of Protein Chemistry, Genentech, Inc., South San Francisco, CA, 94080, USA.
Jasvinder K AtwalDepartment of Neuroscience, Genentech, Inc., South San Francisco, CA, 94080, USA. atwal.jasvinder@gene.com.ORCID http://orcid.org/0000-0001-5995-478X

Funding

Genentech (Genentech, Inc.) N/A
6 · The paper itself

Abstract

The blood-brain barrier (BBB) restricts efficient penetration of systemically delivered therapeutic antibodies into the brain, limiting the development of this class of drugs to treat neurodegenerative diseases. Here we demonstrate that the neonatal Fc receptor (FcRn), which is highly expressed at the BBB, can be used to facilitate IgG transport to the brain. Engineering of the antibody Fc region to promote binding to FcRn at neutral pH enhances antibody transcytosis in a cellular model. In vivo, these modifications improve brain penetration, as well as brain target engagement and activity, of systemically administered antibodies in both mice and non-human primates. This engineering approach can be broadly implemented to enhance central nervous system (CNS) exposure of antibody- and Fc-based drugs, improving the clinical potential of biotherapeutics for the treatment of human brain diseases.

Indexed as

Blood-Brain BarrierHistocompatibility Antigens Class IImmunoglobulin GReceptors, FcAnimalsBiological TransportBrainFemaleHumansImmunoglobulin Fc FragmentsMiceMice, Inbred C57BLTranscytosisFc receptor, neonatalHistocompatibility Antigens Class IImmunoglobulin Fc FragmentsImmunoglobulin GReceptors, Fc

Identifiers

PMID40319060
PMCPMC12049489

What OpenQuestion holds

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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.