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Nanobodies targeting hnRNPA2/B1 and tau
Azady Pirhanov, Cristian Rodriguez, Fatemeh Tashakori-Asfestani, Raven Gonsoulin, Rayne Santiago, Katarnut Tobunluepop, Emmanuella Erhunmwunsee, Sambhavi Puri et al.. bioRxiv : the preprint server for biology, 2025-11-24
Topic: Disease mechanisms in lab and animal studies
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.
Key findings
- Furthermore, fusion to ubiquitin ligase adaptor domains significantly decreased hnRNPA2/B1 and tau levels.
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Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 22 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 13 of the 60 points we could judge it on, which is 22 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv : the preprint server for biology) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41383776) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 13 / 60 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 13 of the 60 points we could judge it on is 22 out of 100. |
| Total | 22 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Pirhanov, A., Rodriguez, C., Tashakori-Asfestani, F., Gonsoulin, R., Santiago, R., Tobunluepop, K., et al. (2025). Nanobodies targeting hnRNPA2/B1 and tau. bioRxiv : the preprint server for biology. https://doi.org/10.1101/2025.11.21.689763
Vancouver
Pirhanov A, Rodriguez C, Tashakori-Asfestani F, Gonsoulin R, Santiago R, Tobunluepop K, et al. Nanobodies targeting hnRNPA2/B1 and tau. bioRxiv : the preprint server for biology. 2025. doi:10.1101/2025.11.21.689763. PMID: 41383776.
BibTeX
@article{pirhanov2025-41383776,
author = {Pirhanov, Azady and Rodriguez, Cristian and Tashakori-Asfestani, Fatemeh and Gonsoulin, Raven and Santiago, Rayne and Tobunluepop, Katarnut and Erhunmwunsee, Emmanuella and Puri, Sambhavi and others},
title = {{Nanobodies targeting hnRNPA2/B1 and tau}},
journal = {bioRxiv : the preprint server for biology},
year = {2025},
doi = {10.1101/2025.11.21.689763},
pmid = {41383776},
url = {https://doi.org/10.1101/2025.11.21.689763}
}
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