Nanobodies are the recombinant antigen binding fragments derived from camelid heavy chain-only antibodies (HCAbs). The serendipitous discovery of functional HCAbs in 19931 opened new avenues for single-domain antibody (sdAb) research and development. Encoded by a single exon, their small size and favorable biophysical properties have enabled sdAbs to increasingly replace conventional antibodies as research tools, as modular building blocks for complex molecular formats, and, more recently, as noninvasive bioimaging probes and therapeutic agents. Many sdAbs display unique functional and biological activities, such as stabilizing specific target conformations or assembly intermediates, inhibiting or activating receptors, or promoting receptor internalization. Moreover, many sdAbs can be functionally expressed as intrabodies inside cells. Super-resolution imaging through reduced linkage error is another application for sdAbs. Initially, nanobodies or sdAbs were retrieved from immune libraries using phage display and bio-panning. Over time, naïve or synthetic libraries and alternative display technologies2,3 expanded the repertoire of discovery platforms.4 More recently, artificial intelligence–based approaches have allowed the de novo design of sdAbs.5
Research over more than 30 years has yielded tens of thousands of well-characterized sdAbs. Yet only a small percentage of them has been described in the scientific literature, and even fewer sequences are publicly available, rendering them effectively invisible -and of little use- to the broader scientific community and emerging AI applications. This has prevented their wider adoption and reuse, leaving many of these valuable binders scientifically dormant and their potential untapped.
Open access to sdAb sequences is essential to advancement of the field. To address this need, a consortium of leaders in the single-domain antibody field established NanoSaurus (www.nanosaurus.org), a curated open-access platform dedicated to preserving, sharing, and unlocking the full potential of these remarkable molecules. A unique identifier is assigned to each sdAb entry that includes its complete amino acid sequence. This makes it possible to reproduce, clone, and independently validate the sdAb. Entries summarize all available validation data and applications. They likewise specify whether the sdAb is animal-derived or synthetic, and refer to relevant publications describing their use. As new information becomes available, these records can be updated to ensure that the database remains interactive, current, and relevant.
By bringing sequence, provenance, and validation data together in a single, searchable resource, NanoSaurus transforms sdAbs from individual, anecdotal laboratory reagents into accessible scientific assets. This will accelerate their reuse, validation, and translation into new research and therapeutic applications.
NanoSaurus also aims to ensure proper recognition of all researchers who contributed to the generation and characterization of sdAbs, an important consideration for early-career scientists. To ensure proper credit, provenance, and traceability, at least one contributing author must provide a verified ORCID identifier. Combined with a unique NanoSaurus accession number, this creates a permanent link between each sdAb, its contributors, and the laboratory from which it originated.
Just as mandatory deposition in the Protein Data Bank6 transformed structural biology by making structural data ‘open access,’ the antibody discovery field now has an opportunity to embrace a similar culture of openness. We hope that journals will adopt the deposition of sdAb sequences in NanoSaurus as a routine requirement for publication. With broad community participation and support, NanoSaurus can become a central repository of curated, annotated, and openly available sdAb information, unlocking the full value of these remarkable molecules for the benefit of the entire scientific community.
Acknowledgments
R.O. thanks the Rosalind Franklin Institute for support. P.D.F., E.P. & J.S. thank Instruct-ERIC, part of the European Strategy Forum on Research Infrastructures (ESFRI), and the Research Foundation – Flanders (FWO) for their support to the Nanobody discovery.
Funding Statement
This work was supported by the Fonds Wetenschappelijk Onderzoek (FWO); Instruct-ERIC; Rosalind Franklin Institute; Medical Faculty, University of Bonn; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation).
Disclosure statement
No potential conflict of interest was reported by the author(s).
Data availability statement
There are no data associated with this letter to the editor.
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Data Availability Statement
There are no data associated with this letter to the editor.