Evidence map›Paper›PMID 41383776›Full record

ArticlebioRxiv : the preprint server for biology2025

Nanobodies targeting hnRNPA2/B1 and tau.

Azady Pirhanov, Cristian Rodriguez, Fatemeh Tashakori-Asfestani, Raven Gonsoulin, Rayne Santiago, Katarnut Tobunluepop, Emmanuella Erhunmwunsee, Sambhavi Puri, Monika Arbaciauskaite, Wu He and 2 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. 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

12 authors.

Azady PirhanovDepartment of Biomedical Engineering, University of Connecticut, Storrs, CT, 06269, USA.
Cristian RodriguezDepartment of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT, 06269, USA.
Fatemeh Tashakori-AsfestaniDepartment of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT, 06269, USA.
Raven GonsoulinDepartment of Anatomy & Neurobiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, 02118, USA.
Rayne SantiagoDepartment of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT, 06269, USA.
Katarnut TobunluepopDepartment of Anatomy & Neurobiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, 02118, USA.
Emmanuella ErhunmwunseeDepartment of Anatomy & Neurobiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, 02118, USA.
Sambhavi PuriDepartment of Anatomy & Neurobiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, 02118, USA.
Monika ArbaciauskaiteDepartment of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT, 06269, USA.
Wu HeFlow Cytometry Facility, Center for Open Research Resources and Equipment, University of Connecticut, Storrs, CT 06269.
Benjamin WolozinDepartment of Anatomy & Neurobiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, 02118, USA.
Yongku ChoDepartment of Biomedical Engineering, University of Connecticut, Storrs, CT, 06269, USA.ORCID 0000-0001-5621-521X

Funding

The role of N6-methyladenosine modified RNA in Alzheimer's disease: Equipment SupplementR01AG080810 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Benjamin L Wolozin, Xiaoling Zhang · 2023 to 2026
$3.2M
A synthetic biology approach for tau post-translational modifications in ADR01AG083876 · NIA · UNIVERSITY OF CONNECTICUT STORRS · PI Yongku Peter Cho, Jesse Rinehart · 2023 to 2026
$2.4M
Nanobodies targeting stress granule componentsR21AG083761 · NIA · UNIVERSITY OF CONNECTICUT STORRS · PI CHO, YONGKU PETER · 2023 to 2023
$461k
NIA NIH HHS R01 AG080810NIA NIH HHS R01 AG083876NIA NIH HHS R21 AG083761
6 · The paper itself

Abstract

Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) is an RNA-binding protein that mislocalizes to the cytoplasm and forms stress-induced granules in tauopathy and multisystem proteinopathy. It also preferentially interacts with oligomeric tau and is required for tau-mediated neurodegeneration in a mouse model of Alzheimer's disease. To study endogenous hnRNPA2/B1 and tau, we generated nanobodies that specifically recognize these proteins. We screened yeast surface display nanobody libraries using an avidity-enhanced screening strategy that enabled selection of binders against short peptide ligands. This led to isolation of anti-hnRNPA2/B1 and anti-tau nanobodies with defined epitopes. Directed evolution of the anti-hnRNPA2/B1 nanobody improved binding affinity by over 20-fold but caused cytoplasmic aggregation, demonstrating a tradeoff between affinity and intracellular behavior. Although the final nanobodies retained modest affinities, they showed robust intracellular colocalization with their targets. Furthermore, fusion to ubiquitin ligase adaptor domains significantly decreased hnRNPA2/B1 and tau levels. Collectively, these nanobodies provide valuable tools for studying hnRNPA2/B1 and tau dynamics in their native cellular context.

Identifiers

PMID41383776
PMCPMC12694600

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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.