VHH Antibody Libraries (Single Domain)
The Stability of a Camelid. The Diversity of a Synthetic.
Biomolecular Discovery Services (BDS) offers premier access to proprietary VHH (single-domain antibody) libraries for therapeutic and diagnostic discovery. Whether you need the natural hypermutation of a naive llama repertoire or the controlled diversity of our synthetic humanized libraries (C6, C7, C8), we provide the high-quality starting material required to find binders for even the most challenging epitopes.
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Why Choose VHH (Nanobodies)?
VHH antibodies (also known as nanobodies) lack the light chain found in conventional IgGs, resulting in a significantly smaller (around 15 kDa) and more stable molecule.
- Tissue penetration: Their small size allows them to cross biological barriers and penetrate dense solid tissues, including difficult compartments such as the blood-brain barrier.
- High stability: VHHs are resistant to extreme pH and temperature, making them ideal for diagnostic kits, ruggedized reagents, and challenging assay conditions.
- Epitope access: The protruding CDR3 loop can access cryptic clefts on enzymes and GPCRs that traditional, flatter IgGs cannot reach.
Our Proprietary VHH Library Options
We offer screening services against two distinct classes of VHH libraries, ensuring we match the right diversity and framework to your target and end use.
1. The Synthetic "C-Series" Libraries (C6, C7, C8)
Our C-series are state-of-the-art synthetic VHH libraries built on a highly stable, humanized scaffold (DP-47 germline). By randomizing the CDR1, CDR2, and CDR3 regions with precise codon usage, we maximize functional diversity while minimizing developability risks.
- Library size: > 3 × 109 (3 billion) variants.
- Scaffold: Humanized framework optimized for high expression and low immunogenicity.
- Design: Tailored amino acid distributions to mimic natural binders without the bias of an immune response.
- Best for: Therapeutic leads requiring human frameworks and targets where immunization is impractical or impossible.
2. Naive Llama VHH Library
Our naive llama VHH library is derived from PBMCs of non-immunized llamas, capturing the natural immune repertoire of the camelid species. It provides access to naturally occurring VHH sequences that have already passed in vivo selection for stability and correct folding.
- Library size: ~1 × 109 variants.
- Source: Natural llama immune repertoire.
- Best for: Reagent and diagnostic development, discovery campaigns that benefit from natural CDR3 diversity, and early-stage hit finding.
The Discovery Process: How We Screen
We do not sell tubes of DNA. We deliver validated binders. Our team performs the biopanning and screening in-house to ensure optimal handling of these complex libraries and to give you actionable results instead of raw materials.
- Target preparation: We validate your antigen format, whether biotinylated protein, purified antigen, peptide, or cell-based presentation.
- Phage display panning: We perform 3–4 rounds of selection using your chosen VHH library, progressively increasing stringency to enrich for specific, high-affinity binders.
- ELISA screening: We screen hundreds of individual clones by ELISA or related assays to verify binding to your target and counter-screen where appropriate.
- Sequencing: Positive hits are sequenced to identify unique families and evaluate sequence liability or redundancy.
- Production: Selected VHHs are expressed in suitable hosts (commonly E. coli or mammalian systems) and delivered as purified protein.
Learn more about our Phage Display Panning Process →
From VHH to Final Format
One of the greatest advantages of the VHH platform is modularity. Once we identify a binder, BDS can engineer it into the format that best fits your therapeutic, diagnostic, or research application.
- VHH-Fc fusions: Extend half-life, enable effector function where desired, and support standard IgG-based detection.
- Bi-specifics and multi-specifics: Link multiple VHHs to target different antigens or to engage effector cells and checkpoints within a single construct.
- Humanization: Further engineer naive llama-derived sequences to reduce immunogenicity while preserving affinity and specificity.
Start Your VHH Campaign
Access the power of single-domain antibodies without the cost and complexity of maintaining a llama herd. Whether you are starting a new discovery campaign or looking to expand an existing program with VHH-based binders, BDS can help you choose the right library and screening strategy for your target.
