Phage Display: Expanding the Search for Novel VHHs
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
High diversity
Broad antigen compatibility
Directed panning
Customizable workflows
Challenging targets
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