VHH Discovery Platform

Unlocking High-Performance VHH Antibodies Through Dual Discovery Routes

At Cortalix, VHH discovery is the foundation of everything we develop.
Our platform combines synthetic VHH antibody libraries, immune libraries, and next-generation cell-free display technologies to deliver fast, reliable, and application-ready binders for imaging, therapeutics, diagnostics, and cell-based engineering.

By integrating these complementary routes, we maximize diversity, affinity, and biophysical quality—ensuring you receive the best possible VHH binder for your target.

Dual Discovery Routes

1. Synthetic VHH Library Platform (humanized, stable, fast)

Our proprietary synthetic VHH libraries are built on highly stable, humanized frameworks with optimized CDR architectures.

Key advantages:

  • Immediate project start — no immunization required

  • Broad sequence diversity engineered for solubility and stability

  • Ideal for toxic, non-immunogenic, or difficult antigens

  • Highly controlled design enabling efficient downstream engineering

Synthetic discovery is the fastest route for early programs requiring design flexibility or rapid initiation.

Figure:

The Cortalix discovery workflow combines immune and synthetic VHH libraries with phage display. After multiple rounds of phage panning and screening, including optional assays on intact cells, unique binders are identified. Clones are validated by ELISA-based affinity measurements and DNA sequencing to ensure optimal candidates for downstream development.

2. Immune Library Platform (natural affinity maturation)

Cortalix maintains high-quality immune VHH libraries generated from immunized llamas.

Strengths:

  • Naturally affinity-matured binders

  • Broad epitope coverage

  • Excellent performance on membrane proteins and complex targets

  • High success rate for advanced or conformational epitopes

Immune discovery is preferred when affinity, specificity, or complex target recognition is essential.

Complementary Cell-Free Ribosomal Display

We are developing a high-diversity ribosomal display system that further expands binder space beyond what phage display alone can reach.
In combination with phage display, this dual system significantly increases the probability of identifying unique, high-performing VHHs.

CDR Grafting & Framework Optimization

  • When top binders come from immune libraries, CDRs can be grafted onto optimized synthetic frameworks.

    Benefits:

    • Improved humanization

    • Increased stability and expression yield

    • Consistent performance across downstream engineering steps

    This ensures every final VHH binder is both biophysically robust and ready for translation.

Why Use These Platforms?

  • Combining synthetic and immune library discovery provides:

    • Maximum epitope coverage

    • Higher probability of success across antigen classes

    • Superior diversity and binder quality

    • Flexible project design tailored to the target

    This dual‑platform approach strengthens downstream applications such as MultiDome™ multispecifics, AlbuFlex™ half‑life extension, and CARVex™ nanobody-based CAR-T targeting.

Discovery Workflow

Our standard discovery workflow includes:

  • Antigen QC & preparation

  • Library selection (synthetic, immune, hybrid)

  • Phage display panning — including optional cell-based panning

  • High-throughput clone screening

  • Binding validation (ELISA/Octet)

  • Sequence analysis & developability assessment

  • Optional reformatting (bivalent, Fc-fusion, NIR-labeling)

The entire workflow is modular and can be adapted to any project design.

Deliverables

Typical project outputs include:

  • Validated VHH antibody sequences

  • Purified VHH proteins (optional)

  • Full binding dataset and QC report

  • Developability assessment

  • Optional reformatting into bivalent, trivalent, Fc-fusion, or imaging-ready constructs

From Discovery to Application

VHHs generated in this platform seamlessly feed into Cortalix’s engineering suite:

  • MultiDome™ — Multispecific engineering

  • AlbuFlex™ — Albumin-binding half-life extension

  • CARVex™ — VHH-based CAR-T targeting

  • NIR imaging probes

  • Assay and ELISA development

This ensures a smooth path from binder discovery to translational application.

Tailored for Industry and Academia

Cortalix provides flexible partnership structures, ranging from fee‑for‑service projects to collaborative programs. Our Discovery Platform is designed for:

  • Biotech and pharma target discovery programs

  • Imaging probe development groups

  • CAR‑T and cell therapy teams

  • Translational research institutes

Start your VHH discovery project

Contact us to discuss your target, project design, or antigen strategy. We help you select the optimal discovery route, synthetic, immune, or a hybrid approach, to ensure strong outcomes and fast progression toward application-specific engineering.