Ribosomal Display for VHH Nanobody Discovery

Access ultra-high VHH library diversity for efficient discovery of novel Nanobody binders

Cortalix provides ribosomal display for the discovery and selection of VHH Nanobodies from highly diverse synthetic libraries. As a cell-free selection technology, ribosomal display enables screening of substantially larger molecular libraries than conventional cell-based display methods.

Our ribosomal display platform provides access to a functional VHH diversity exceeding 10¹³ variants and can be integrated with phage display, screening and downstream VHH engineering to efficiently identify high-quality binders against challenging targets.

Why Ribosomal Display for VHH Discovery?

The probability of identifying high-quality VHH binders depends strongly on the molecular diversity that can be explored during discovery.

Traditional phage display is a powerful and well-established VHH discovery technology, but library size is ultimately constrained by bacterial transformation efficiency. Ribosomal display is entirely cell-free and therefore allows substantially larger libraries to be generated and screened.

At Cortalix, ribosomal display provides access to more than 10¹³ functional VHH variants, creating a very large starting space for VHH Nanobody discovery.

This can be particularly valuable for challenging targets, rare binding solutions or projects where high sequence diversity is desirable.

Cortalix Ribosomal Display Workflow

Synthetic VHH Library → Ribosomal Display → Enrichment → Phage Display / Screening → Sequence Identification → VHH Characterization

Cortalix combines ribosomal display with its existing VHH discovery and engineering capabilities. Highly diverse synthetic VHH libraries are subjected to iterative selection against the target of interest. Enriched populations can subsequently be transferred into downstream screening and characterization workflows.

Depending on the project, ribosomal display can be used as a primary discovery technology or combined with phage display to exploit the advantages of both approaches.

The resulting VHH candidates can subsequently be expressed, screened and characterized for binding and developability.

Built on the Cortalix VHH Discovery Platform

Our synthetic libraries are based on optimized VHH frameworks, including the Cortalix FC8™ framework, designed for stability, humanization and downstream development.

The platform combines:

• Ultra-high-diversity synthetic VHH libraries
• Ribosomal display
• VHH phage display and panning
• Binder screening and sequencing
• Recombinant VHH expression
• Affinity characterization
• VHH humanization and engineering
• Multispecific VHH development
• Half-life extension and other downstream engineering strategies

This integrated approach allows discovery strategy to be adapted to the biological target and intended application rather than relying on a single selection technology.

Ribosomal Display or Phage Display?

Both technologies can be highly effective for VHH discovery.

Phage display provides a robust and proven platform for iterative selection, clone isolation and screening.

Ribosomal display removes the transformation bottleneck and provides access to much larger library diversity.

Rather than treating the technologies as alternatives, Cortalix can combine ribosomal and phage display within a single VHH discovery strategy. This provides access to very large initial diversity while retaining the practical advantages of phage-based selection and downstream screening.

From VHH Discovery to Lead Candidates

Identifying a binder is only the first step.

Cortalix supports projects from initial target evaluation and VHH discovery through screening, expression, characterization and further engineering. Selected VHHs can subsequently be developed into mono-, bi- or multispecific constructs and adapted for applications including therapeutic targeting, molecular imaging, radioligand therapy, CAR-T targeting and bioanalytical assays.

Start a VHH Discovery Project

Looking for VHH Nanobodies against a new or challenging target?

Contact Cortalix to discuss the most appropriate discovery strategy for your project.