Yeast Display Services for Antibody Discovery & Protein Engineering

Yeast Surface Display for Protein Engineering and Directed Evolution

Beyond Discovery: Optimizing Protein Stability, Affinity, and Functionality. While many platforms focus solely on finding binders, Ranomics specializes in protein engineering services that refine your candidates for real-world therapeutics and industrial applications

Key Service Pillars

• Affinity Maturation: Utilize targeted CDR mutagenesis to increase binding affinity for optimal applications.

• Stability & Solubility Enhancement: Identify variants with superior thermal stability and folding efficiency, critical for manufacturing.

• Epitope Mapping & Binning: High-resolution mapping to understand the exact binding landscape of your engineered proteins.

• Specificity Profiling: Engineering out cross-reactivity to ensure high-target specificity and reduced off-target effects.

• AI/ML guidance: Implement AI/ML pipelines to identify candidates ready for the next phase of your program.

Comprehensive Solutions for Antibody Discovery and Protein Engineering

• Custom Yeast Display Library Construction

• Accelerate your project with libraries designed for maximum functional diversity. We specialize in buildling high-quality, stable libraries tailored to your specific target requirements

• Library Formats: Expert construction of scFv, Fab, VHH (nanobody), and non-antibody scaffold libraries

• High Diversity: Optimized transformation protocols yielding diversities of 10e9 to 10e10 independent clones

• Smart Design: Incorporation of codon optimization and specialized leader sequences for enhanced surface expression

• High-Throughput Selection & Screening

• Move beyond traditional panning with our precision driven screening platform

• FACS-Based Sorting: Multi-parameter flow cytometry allows for real time discrimination of clones based on affinity, expression level and specificity.

• Stringent Selection: Ability to isolate rare, high-affinity binders from massive background populations.

• Negative Selection: Integrated "de-selection" steps to eliminate cross-reactive or non-specific binders early in the process

• Advanced Protein Engineering & Affinity Maturation

• Optimize your existing leads for therapeutic-grade and market-grade performance

• Directed Evolution: Generation of secondary libraries via error-prone PCR or site-saturation mutagenesis to "walk" the fitness landscape

• Stability Engineering: Selection for improved thermal stability and resistance to aggregation - critical for manufacturability.

• pH-Sensitive Binding: Engineering variants that exhibit specific binding profiles under varying physiological conditions

A Proven, Data-Drive Process for Protein Engineering and Discovery

Step 1: In-silico Design & Library Synthesis

We begin by utilizing AI-driven design tools to optimize your library for functional diversity and expressibility. This step minimizes non-functional variants and ensures a robust starting population for selection

• Codon Optimization: Sequences are tailored for high-level expression in specific yeast strains

• Synthesis Precision: High-fidelity DNA synthesis ensures accurate representation of the designed diversity

Our Streamlined workflow is engineered to maximize efficiency while maintaining the highest standards of data integrity. By integrating advanced design with high-throughput laboratory validation, Ranomics provides a transparent path from initial sequence to a characterized lead candidate.

Step 2: High Efficiency Transformation

Using proprietary protocols, we transform the library into our specialized yeast display strains. This process is optimized to achieve the massive scale necessary for comprehensive repertoire coverage.

• Scale: Guaranteed transformation efficiency to maintain libary diversities up to 10e10

• Quality Control: Every library is validated for size and sequence integrity before entering the screening phase.

Step 3: Iterative Selection via FACS

Our yeast display platform utilizes fluorescence-activated cell sorting (FACS). This allows us to visualize the entire population and precisely gate for the highest affinity binders

• Clones are sorted based on binding equilibrium and dissociation rates

• Simultaneous screening for expression, affinity, and cross-reactivity

Step 4: NGS Validation and Lead Characterization

Using next-generation sequencing, we analyze the enriched pools to identify the most promising candidates and evaluate their fitness profiles

• Bioninformatics: Comprehensive analysis of enrichment ratios and sequence motifs

• Confirmation: Top-performing clones are expressed and validated via ELISA or SPR to confirm binding kinetics

Specialized Applications: From Discovery to Industrial Optimization

Ranomics’ Yeast Display platform is the industry standard for high-throughput discovery and the intensive engineering of robust protein scaffolds. Our platform is specifically optimized for applications requiring massive library coverage and rapid iterative selection.

Nanobody (VHH) & scFv Discovery

Yeast display is the premier platform for small-format antibody discovery. Because yeast can be transformed at significantly higher efficiencies than mammalian cells, we can screen much larger libraries to identify rare, high-affinity binders that other platforms might miss.

Directed Evolution of Industrial Enzymes

Beyond therapeutic antibodies, our yeast platform is a powerful tool for the directed evolution of enzymes. We engineer proteins to withstand harsh industrial conditions, including extreme pH, high temperatures, and organic solvents.

Engineering cytokines and growth factors requires a eukaryotic folding environment that can handle disulfide bond formation and glycosylation. Yeast display provides this environment at a fraction of the cost and time of mammalian cell culture.

Cytokine and Recombinant Protein Engineering

Frequently asked questions

What is the typical library size for a custom yeast display project?

We routinely achieve transformation efficiences that rseult in library diversities of 10e9 and 10e10 unique variants. This massive scale is essential for discovering rare high-affinity binders and exploring a vast sequence space during protein engineering

How does yeast display compare to phage display for antibody discovery?

While phage display is a valuable tool, yeast display offers several key advantages, including eukaryotic post-translational modifications, superior folding for complex proteins, and the ability to use FACS for quantitative, real-time selection of candidates based on affinity and stability.

What are the standard deliverables for a yeast display service?

Our standard data package includes a comprehensive report featuring FACS enrichment plots, NGS sequence analysis of the final pools, relative affinity measurements for top leads, and the delivery of expression-ready plasmids for your top candidates

Can you optimize an existing lead candidate for better stability?

Yes. Our protein engineering service specialize in affinity maturation and stability enhancement. We can take your existing sequence, generate a focused secondary library, and select for variants that show improved thermal stability and reduced aggregation.

Ready to Accelerate Your Protein Engineering Project?

Partner with Ranomics to leverage the full power of yeast surface display. Whether you are starting with a new target or looking to optimize a lead candidate, our technical team is ready to help you achieve your milestones faster.