Phage Display: Expanding the Search for Novel VHHs

An in vitro selection technology linking genes to proteins. At Isogenica, enhanced phage display screens up to 10¹² variants to discover novel VHH binders
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How it works

Phage display is an in vitro selection technology that links genotype to phenotype by displaying antibody fragments on the surface of bacteriophages. When VHH genes are inserted, each phage presents a corresponding antibody fragment, creating a direct connection between sequence and protein. 

This enables the construction of very large libraries—up to 10¹² variants—that can be screened against a target antigen through “biopanning.” Phages displaying VHHs with affinity are captured while non-binders are removed. Bound variants are eluted, amplified, and sequenced, generating a panel of candidate binders for further optimisation. 

Since the 1990s, phage display has been central to antibody discovery, underpinning therapeutics such as adalimumab (Humira®). Its capacity to interrogate vast sequence space makes it invaluable for both initial discovery and affinity maturation. 

At Isogenica, phage display complements our proprietary CIS Display™ platform. CIS Display™ offers ultra-high diversity libraries (up to 10¹⁴), while phage display provides a proven, widely adopted route for VHH discovery. Integrated with our synthetic libraries, the two systems deliver flexible discovery strategies that balance diversity, speed, and downstream developability

 

Key Advantages of Phage Display

Rapid timelines

Panning and screening completed in 4–6 weeks 

High diversity

Supports libraries of up to 10¹² variants

Broad antigen compatibility

Suitable for a wide range of target types

Directed panning

Strategies to select for pH dependency, species cross-reactivity, isoform specificity, or cell binding 

Customizable workflows

Adaptable for bespoke libraries and affinity maturation 

Challenging targets

Effective with toxic, highly conserved, and intracellular proteins 

At Isogenica, we apply phage display to:

  • Discover novel VHHs for diverse and challenging targets
  • Improve leads through affinity maturation to enhance binding strength and specificity
  • Engineer VHHs to optimise existing antibody fragments
  • Support therapeutic and diagnostic applications across oncology, inflammation, and infectious disease research

FAQs

How does phage display differ from CIS Display™?

Phage display depends on bacterial replication and is typically limited to 10⁹–10¹⁰ variants, while CIS Display™ is cell-free and supports much larger library sizes. 

Can you work with our existing phage library?

Yes. We can validate phage-derived hits or run dual-platform campaigns alongside our synthetic libraries. 

Why does Isogenica still offer phage display alongside CIS Display™?

Phage display remains valuable for orthogonal validation, comparative discovery, and specific workflows where bacterial display is advantageous. 

Not sure which platform suits your target class?

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