AbNano™ VHH Naïve Library

The Problem with Predictive Diversity

Our AbNano™ VHH Naïve Library is built from natural camelid immune repertoires to maximize protein-level diversity and unlock binders against a wide range of therapeutic targets. Delivered ready to pan, it is the fastest way to start discovering novel, high-affinity VHHs without the complexity of building a library yourself. By starting with nature’s own diversity, AbNano gives discovery teams an authentic and adaptable platform. The result is a tool that fits seamlessly into existing workflows while expanding the range of what is possible in therapeutic antibody development.

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Why AbNano

Small. Stable. Specific.

Ribbon diagram of a VHH nanobody protein structure highlighting beta-sheet folds and compact single-domain architecture.

Easy to Use

Delivered ready to pan so you can start discovery immediately.
No cloning or library construction required.
Single-domain format simplifies workflows and downstream engineering.

Freedom to Operate

Delivered ready to pan so you can start discovery immediately.
No cloning or library construction required.
Single-domain format simplifies workflows and downstream engineering.

Versatile Discovery Tool

Delivered ready to pan so you can start discovery immediately.
No cloning or library construction required.
Single-domain format simplifies workflows and downstream engineering.

Scientific Support

Delivered ready to pan so you can start discovery immediately.
No cloning or library construction required.
Single-domain format simplifies workflows and downstream engineering.

Technical Overview

How It's Constructed

The AbNano™ VHH Naïve Library is constructed from 103 naïve camelids (77 llamas and 26 alpacas). More than 1.51 × 10¹⁰ PBMCs were collected and processed using our proprietary workflows for RNA isolation, cDNA synthesis, and PCR amplification. Transformants were screened and validated by Sanger and next-generation sequencing, with 89% of VHH sequences in-frame.

Library Size: 1.12 × 10¹⁰ CFU
Delivery format: 1 mL aliquots at 10¹¹ PFU/mL, ready to pan
Custom formats: Available on request

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Histogram of CDR3 cluster lengths in a naïve VHH nanobody library showing amino acid length distribution.

AbNano™ VHH Naïve Library Performance & Validation

To demonstrate the discovery power and performance of the AbNano™ Naïve VHH library, we conducted representative phage display panning campaigns against several biologically relevant targets.

These included two extracellular domains of receptor tyrosine kinase complexes, the insulin receptor (INSR) β isoform and the epidermal growth factor receptor (EGFR) canonical isoform, as well as the immune checkpoint protein PD-L1, an important cancer biomarker.

After three rounds of selection, 94 random clones were screened by ELISA, and high-signal candidates were further characterized for binding activity.

The AbNano Naïve VHH library consistently produces nanomolar binders against challenging targets, including proteins, peptides, VLPs, and live cells. Its natural diversity supports broad discovery campaigns and enables rapid hit generation.

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Who benefits

Biopharma, biotech, and academic teams developing immune-targeted therapeutics or diagnostics gain a direct path to validated, functional VHHs. The AbNano™ Naïve VHH Library supports reproducible hit identification and integrates seamlessly into discovery, engineering, and preclinical development workflows.

Modular, Versatile, And Engineerable VHH Domains

AbNano VHH antibodies offer human-like frameworks and CDR3 length distributions close to human IgHV3-23. This simplifies humanization and downstream development. Their small size enables rapid clearance, while PK/PD profiles can be tuned through covalent and non-covalent engineering.

This flexibility enables:

Binding to new epitopes or complementing existing therapeutics

Development of bispecific and biparatopic formats

Optimization of pharmacokinetics and tissue distribution

AbNano™ has already yielded nanomolar-affinity VHH binders to key therapeutic targets including PD-L1, EGFR, and INSR-β. These validated results demonstrate its potential as a discovery engine for next-generation therapeutics.

AbNano™ VHH Naïve Library Specifications

The library was constructed from 103 naïve animals: 77 llamas and 26 alpacas. A total of 1.51 x 10¹⁰ PBMC cells were collected and used for library construction.

Libraries were constructed following Abcore's internal workflows for RNA isolation, cDNA synthesis, and PCR amplification using species-specific primers. Transformants were analyzed initially by Sanger sequencing.

Sanger analysis demonstrated 89% of VHH sequences in-frame. The library was subsequently analyzed by next generation sequencing methodology. Reads were clustered and analyzed for diversity and confirmed to meet our QC standards.

The total number of transformants for the library was 1.12 x 10¹⁰ CFU. Library bacterial stocks were grown to log phase, infected by M13KO7, PEG precipitated, and the pooled phage was titered. Phage were normalized in PBS + 20% glycerol and aliquoted as 1 mL tubes frozen and stored at -80 °C. The library is delivered as 1 mL aliquots.

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Nanomolar VHH binders of PD-L1 and Other Therapeutic Targets from the AbNano™ VHH Naïve Library

Discovering novel VHH domains can take place by multiple workflows, including using B-cell sorting and using display libraries. In this poster, we present the construction and validation of the AbNano™ VHH Naive Library, a large naïve library from llamas and alpacas

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Scientific poster showing discovery of nanomolar PD-L1 VHH binders using the AbNano™ VHH naïve antibody library.