Antibody Aptamer Screening Service

What is an Antibody Aptamer Screening Service?

It is a specialized contract research service where a biotechnology company uses SELEX (Systematic Evolution of Ligands by EXponential Enrichment) or advanced variations of it to discover and develop aptamers that bind with high affinity and specificity to a target antibody.

• Antibody: A large, Y-shaped protein produced by the immune system to identify and neutralize pathogens.

• Aptamer: A short, single-stranded DNA or RNA oligonucleotide (or a modified derivative) that folds into a specific 3D structure, enabling it to bind to a target molecule with antibody-like specificity. Often called “chemical antibodies.”

The goal of the service is to provide clients with synthetic, recombinant-like binding molecules as alternatives or complements to traditional monoclonal antibodies.

Why Screen for Aptamers Against Antibodies?

Aptamers offer distinct advantages, making them attractive for various applications:

1. Anti-Drug Antibody (ADA) Detection: Develop aptamer-based assays to detect and quantify ADAs in clinical trials for biotherapeutics.

2. Diagnostic Tools: Create aptamer sensors (aptasensors) to detect specific antibody biomarkers for diseases (e.g., autoantibodies in autoimmune disorders).

3. Therapeutic Neutralization: Discover aptamers that can bind and neutralize pathological antibodies (e.g., in autoimmune diseases like lupus or myasthenia gravis).

4. Purification & Pull-Down: Use aptamers as ligands in chromatography or in assays to capture and isolate specific antibodies from complex mixtures.

5. Research Reagents: Develop stable, reproducible aptamer reagents for research use, often with lower batch-to-batch variation than some antibodies.

Typical Workflow of a Screening Service

A reputable service provider will follow a rigorous, multi-stage process:

Phase 1: Project Design & Library Selection

• Consultation: Define the target (specific antibody, isotype, region – e.g., Fab, Fc), desired affinity (Kd), specificity (cross-reactivity requirements), and application.

• Library Design: Choose from standard (naïve) DNA/RNA libraries or advanced libraries containing modified nucleotides (e.g., SOMAmers with protein-like side chains) for enhanced diversity and stability.

• Selection Strategy: Decide on the SELEX method (e.g., Capture-SELEX, Magnetic Bead SELEX, CE-SELEX) and design counter-selection steps to eliminate binders to common off-targets (e.g., the antibody’s constant region, assay plates, carrier proteins).

Phase 2: The SELEX Process (The Core Screening)

• Incubation: The oligonucleotide library is incubated with the immobilized target antibody.

• Partitioning: Unbound sequences are washed away; bound sequences are eluted.

• Amplification: The eluted bound sequences are amplified by PCR (for DNA) or RT-PCR (for RNA).

• Iteration: This cycle is repeated (typically 8-15 rounds) under increasingly stringent conditions to enrich the pool for high-affinity, specific binders.

• Monitoring: Binding enrichment is tracked after each round using quantitative PCR or other methods.

Phase 3: Candidate Identification & Characterization

• Next-Generation Sequencing (NGS): The enriched pool from the final SELEX round is sequenced. Bioinformatic analysis identifies unique, enriched sequence families.

• Synthesis & Cloning: Lead candidates from dominant families are chemically synthesized.

• Primary Characterization:

  • Affinity Measurement: Determine dissociation constant (Kd) using techniques like Surface Plasmon Resonance (SPR), BLI (Bio-Layer Interferometry), or EMSA.

  • Specificity Testing: Test against related antibodies, isoforms, and irrelevant proteins.

  • Miniaturized Functional Assay: A simple test relevant to the end application (e.g., ELISA-style detection).

Phase 4: Delivery & Reporting

• The client receives a detailed report and the sequences of the lead aptamer candidates.

• Deliverables often include:

  • Lyophilized, purified aptamers.

  • Full characterization data (Kd, specificity, suggested buffer conditions).

• Optional Advanced Services: Further truncation (minimization), site-specific modification (biotin, dyes, PEGylation), stability testing, and assay development support.

Key Considerations When Choosing a Service Provider

Leading Providers in the Field

The market includes both specialized aptamer companies and broad CROs:

• Aptamer Group (UK)

• AptaDiscovery (France)

• Aptagen, LLC (US)

• Base Pair Biotechnologies (US)

• AMSBIO (Aptamer Services)

• TriLink BioTechnologies (Aptamer Discovery Services)

• Many university core facilities and research institutes also offer collaborative SELEX services.

Conclusion

An Antibody Aptamer Screening Service provides a pathway to acquire highly specific, chemically synthesized binding molecules. By outsourcing to experts with specialized libraries, advanced SELEX platforms, and robust characterization tools, researchers can efficiently develop powerful aptamer reagents for diagnostics, therapeutics, and biotechnology applications, leveraging the unique benefits of aptamers over traditional antibodies.