Evidence map›Paper›PMID 42649418›Full record

ArticleNature chemical biology2026

CA-IV-directed small-molecule shuttle enables targeted brain delivery of biologics.

Xiaozhe Ding, Xinhong Chen, Philip Boehm, Alba Carretero-Cerdán, Seongmin Jang, Erin E Sullivan, Cynthia M Arokiaraj, Fiona Ristic, Bill C Kavvathas, Lillian J Campos and 9 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature chemical biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Xiaozhe Ding *Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA. xding@caltech.edu.ORCID http://orcid.org/0000-0002-0267-0791
Xinhong Chen *Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.ORCID http://orcid.org/0000-0003-0408-0813
Philip Boehm *Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA.
Alba Carretero-Cerdán *Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA.
Seongmin JangDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.ORCID http://orcid.org/0000-0002-9822-6790
Erin E SullivanDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.ORCID http://orcid.org/0000-0002-1724-6520
Cynthia M ArokiarajDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Fiona RisticDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Bill C KavvathasDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Lillian J CamposDepartment of Psychology and National Biomedical Research Institute, University of California, Davis, Davis, CA, USA.
Jitendra SharmaDepartment of Psychology and National Biomedical Research Institute, University of California, Davis, Davis, CA, USA.
Shawn KambojDepartment of Psychology and National Biomedical Research Institute, University of California, Davis, Davis, CA, USA.ORCID http://orcid.org/0000-0003-1343-7618
Yaping LeiDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Mona ShahgholiDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA.
Danielle MantinDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA.ORCID http://orcid.org/0000-0001-8576-3549
Andrew S FoxDepartment of Psychology and National Biomedical Research Institute, University of California, Davis, Davis, CA, USA.
Timothy F ShayDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.ORCID http://orcid.org/0000-0001-6591-3271
Sarah E ReismanDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA. reisman@caltech.edu.
Viviana GradinaruDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA. viviana@caltech.edu.ORCID http://orcid.org/0000-0001-5868-348X

Funding

National Institute on Aging (NIA) ColonyP51OD011107 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Simon J. Atkinson · 2012 to 2026
$191.5M
Chemical Synthesis of Chiral Bioactive MoleculesR35GM118191 · NIGMS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI Sarah Elizabeth Reisman · 2016 to 2026
$6.6M
Engineered AAV Identification, Validation, and Dissemination Pipeline for Brain Cell Type-Specific Manipulation Across SpeciesUF1MH128336 · NIMH · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI FOX, ANDREW S, GRADINARU, VIVIANA · 2021 to 2021
$6.1M
NIGMS NIH HHS R35 GM118191Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) P500PN_210720U.S. Department of Health &Human Services | National Institutes of Health (NIH) DP1OD025535U.S. Department of Health &Human Services | National Institutes of Health (NIH) P51OD011107U.S. Department of Health &Human Services | National Institutes of Health (NIH) R35GM118191U.S. Department of Health &Human Services | National Institutes of Health (NIH) UF1MH128336Vetenskapsrådet (Swedish Research Council) VR-2022-06175
6 · The paper itself

Abstract

The blood-brain barrier (BBB) presents a challenge for central nervous system (CNS) therapies. Receptor-mediated transcytosis offers a solution, but existing receptor targets are ubiquitous across CNS and peripheral tissues, causing unintended exposure. We identified carbonic anhydrase IV (CA-IV) as a brain-enriched receptor enabling engineered viral capsids to cross the BBB. However, it is unclear whether CA-IV can also mediate non-viral delivery. We thus designed a reactive small-molecule shuttle, derived from an FDA-approved binder, that couples to proteins and oligonucleotides in a single step. We validated the binding of conjugated molecules to multiple mammalian CA-IV orthologs and subsequent internalization in cell-based assays. After systemic dosing, CA-IV-targeted antibody conjugates crossed the BBB in mice and neonatal macaques, preferentially accumulating in the brain and sustaining parenchymal levels for at least 7 days. This BrainCAB (Brain access through Carbonic Anhydrase-binder Bioconjugation) technology offers a compact, modular shuttle for selective and prolonged CNS delivery of large molecules.

Identifiers

PMID42649418

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.