Synthetic VHH Libraries: Unmatched Diversity, On Demand
Our synthetic libraries combined with our discovery expertise enable rapid, tailored selection retaining high diversity during screening, without the need for animal immunisation.
Want access to our vast libraries?
Unmatched diversity
Accelerate your antibody discovery research with access to the world’s largest synthetic VHH libraries
VHHantage™
LlamdA®
Ultra-high diversity CDRs based on original llama frameworks. Equivalent to the circulating immune repertoire of 1 million llamas and built using Colibra® technology for reduced CMC liabilities.
HuLlamdA®
White Paper “Data-Driven Validation of Synthetic VHHs”
Designed for biotech and pharmaceutical scientists, this white paper demonstrates how our libraries enhance and accelerate drug discovery, particularly in oncology and immunotherapy
When it comes to synthetic DNA libraries, size matters. In a recent review*, the author concluded that, of all the advances in phage display over the past 30 years, library size really correlates with improved affinity is library size.
Larger, more diverse libraries increase the number of unique sequences available for screening, improving the chances of identifying novel binders with desirable properties.
Our ultra-high diversity VHH libraries offer greater flexibility in antibody discovery, enabling the exploration of multiple target surfaces within a single campaign, as well as the identification of binders against challenging targets and conformations that may be difficult to access through animal immunisation. This opens up new opportunities to discover unique binders with desirable properties and greater potential for freedom to operate.
Not sure which is the right discovery route for your library screen?
Synthetic libraries for faster discovery
Due to the in vivo phenomenon of somatic hypermutation, it is easier to generate VHHs with extremely high affinities (picomolar range) from animal immunisations. Typically, leads from Isogenica’s synthetic libraries have low nanomolar affinities, which are optimal for drug development.
Quicker, cheaper, fewer liabilities
Immunisation of a large animal such as a llama or alpaca takes a lot of target antigen, and a long time. A good immune library can only be made after several months of waiting, boosting, and titre checking, and can take up to 8 months. In contrast, synthetic libraries can be mined immediately.
Furthermore, llama-derived hits require humanisation and may contain high-risk CMC liabilities such as extra cysteine residues or glycoslation sites. Isogenica’s libraries are built using methods designed to reduce the frequency of these liabilities and reduce the downstream engineering work required to turn immune-derived VHHs into potential drugs.
State-of-the-Art Technology
Tailored Display Strategies for Your Discovery Goals
Run all 3 libraries in parallel, adopting the most appropriate selection strategy, depending on your programme’s complexity and timelines.
At Isogenica, we adapt our discovery platform to your targets, selection requirements, and project needs – whether you require streamlined, high-throughput discovery or more complex campaigns requiring specialized antigen presentation.
Our platform offers:
- A robust and adaptable selection workflow that supports both streamlined discovery workflows and more complex, tailored campaigns
- Up to 10¹⁰ phage display efficiency enabling exploration of highly diverse sequences
- The running of 6-10 selection streams per target, allowing multiple selection conditions and strategies to be explored in parallel
- Broad conditions range (e.g. pH, specialized buffers, salinity)
- Flexible antigen presentation, with selection strategies supporting soluble proteins, nanodiscs, and cell-based formats. This enables campaigns to be adapted for more challenging targets such as GPCRs
- Incorporation of next-generation sequencing (NGS) to provide deeper insight into selection outputs and enable more precise identification and prioritization of enriched sequences
- Exclusive IP on up to 5 selected leads
Exclusive IP on up to 5 selected leads
FAQs
What makes your synthetic libraries unique?
Isogenica has built fully synthetic, humanized VHH libraries using structure-guided CDR diversification and human framework design. Combined with our cell-free CIS Display™ technology, they deliver ultra-high diversity and rapid, high-fidelity screening.
How do synthetic and natural libraries differ?
Natural libraries depend on animal immune responses and are constrained by biological variability. Synthetic libraries enable broader, controllable diversity and improved developability.
Do you sell your VHH libraries off-the-shelf?
No. Our libraries are operated in-house to ensure controlled quality and reproducibility.
Can you generate VHHs against a specific antigen for diagnostic purposes?
Yes. We routinely perform targeted campaigns for diagnostic and research applications. Regulated IVD use may require additional validation.
Explore the science behind our antibody discovery platforms
White Paper “Data-Driven Validation of Synthetic VHHs”
This white paper provides a data-driven validation of Isogenica’s synthetic VHH libraries, powered by Colibra® technology. Designed for biotech and pharmaceutical scientists, it demonstrates how these libraries enhance and accelerate drug discovery, particularly in oncology and immunotherapy. Download Extending half-lives of VHH antibodies
Because VHHs are small, they can be cleared quickly from the bloodstream. This can be a useful feature for some applications, but often a longer plasma half-life is desirable. DOWNLOADAdvantages of VHH in bi-specifics
To learn more about the application of VHHs in bi-specifics, we have condensed our expertise into a downloadable Application Note. DOWNLOADOptimizing CAR-T and T-cell antibody engagers: a role for VHH single domain antibodies
This whitepaper summarises the clinical and research landscape for CAR-T and T-cell engaging antibody therapies and show how single domain VHH antibodies can be applied to optimise the next generation of these important new therapeutic modalities. DOWNLOADIsogenica’s PD-L1 VHH as Functional Antagonists
PD-1 is an immune checkpoint protein expressed on the surface of multiple types of immune cells, including antigen-stimulated T-cells and tumour specific T-cells1. Interaction between PD-1 and its ligands (PD-L1 or PD-L2), is responsible for the regulation of T-cell activation, apoptosis, proliferation and cytokine production. DOWNLOADAnti-LRP5/6 VHH inhibits WNT pathway and prevents tumour growth
VHH are the variable domain of heavy chain only antibodies. They are small in size (~15 kD) and biophysically robust. With tunable half-lives, these antibodies are ideal for targeting inaccessible epitopes, achieving enhanced tissue penetration, multi-target binding and formatting for payload delivery… DOWNLOAD