X-Aptamer Screening Services

What is an Aptamer?

First, a quick reminder: Aptamers are short, single-stranded DNA or RNA oligonucleotides that bind to a specific target with high affinity and specificity. They are often called “chemical antibodies.”

The Core Service: SELEX (The Screening Process)

The service revolves around executing a SELEX (Systematic Evolution of Ligands by EXponential enrichment) campaign. This is an iterative, in-vitro combinatorial chemistry process that screens a vast random library (10^14 – 10^15 unique sequences) to find the few that bind your target.

A standard SELEX workflow includes:

1. Library Design & Synthesis: Creating the initial random oligonucleotide pool.

2. Incubation: The library is exposed to the target.

3. Partitioning: Bound sequences are separated from unbound ones (the most critical step, varying by target type).

4. Amplification: The bound sequences are amplified (usually by PCR for DNA, RT-PCR for RNA).

5. Counter-Selection (Negative Selection): To increase specificity, the pool is exposed to non-target surfaces (e.g., immobilization matrix, related proteins) to remove non-specific binders.

6. Repetition: Steps 2-5 are repeated for 8-15 rounds until a high-affinity pool is enriched.

7. Cloning & Sequencing: The final pool is cloned, and individual aptamer sequences are identified via Next-Generation Sequencing (NGS).

8. Bioinformatics & Analysis: NGS data is analyzed to identify candidate sequences, often clustered into families based on sequence/structure motifs.

9. Characterization: Top candidates are synthesized and tested for binding affinity (Kd), specificity (against off-targets), and sometimes minimal functional sequence (truncation).

Types of X-Aptamer Screening Services (By Target “X”)

Services are often specialized based on the target’s nature:

1. Protein Aptamer Services: For purified recombinant proteins, kinases, cytokines, etc. (Most common).

2. Small Molecule Aptamer Services: For toxins, drugs, metabolites. Challenging due to small size; often requires immobilization strategies.

3. Whole Cell-SELEX (or Cell-SELEX): Targets aptamers to specific cell types (e.g., cancer cells, stem cells). Crucial for identifying markers on native cell surfaces without prior knowledge of the target protein.

4. Tissue-SELEX: A more complex variant of Cell-SELEX.

5. Virus/Bacterium SELEX: For intact pathogens or viral particles.

6. In Vivo SELEX: Direct screening within a living animal model to account for physiological complexity. A cutting-edge service offered by few.

Key Technologies & Methodologies Used

Service providers differentiate themselves with their partitioning methods:

• Magnetic Bead-Based SELEX: Target is immobilized on magnetic beads for easy separation. Very common for proteins.

• Nitrocellulose Filter SELEX: Binds protein-aptamer complexes. Simple but less versatile.

• Capillary Electrophoresis (CE-SELEX): Highly efficient, solution-phase selection. Excellent for achieving high affinity quickly.

• Microfluidic SELEX (M-SELEX): Automates the process, uses minimal reagents, and enables precise control.

• Toggle-SELEX: Develops aptamers that cross-react with targets from different species (e.g., human and mouse).

• Capture-SELEX: Useful for small molecules where direct immobilization is problematic.

What to Expect from a Service Provider (Deliverables)

A full-service contract typically includes:

• Project Consultation: To determine feasibility and design the SELEX strategy.

• The SELEX Campaign: Execution of the rounds.

• NGS & Bioinformatics Report: Providing the top 10-20 candidate sequences with cluster analysis.

• Initial Characterization Data: For 2-5 lead candidates, including:

  • Kd (Dissociation Constant): Measured via BLI (Biolayer Interferometry), SPR (Surface Plasmon Resonance), or MST (MicroScale Thermophoresis).

  • Specificity Profile: Binding to related targets or in complex mixtures.

• Aptamer Synthesis: Milligram quantities of the final, chemically modified aptamers (e.g., with biotin, fluorescein, or nuclease-resistant modifications like 2′-F or 2′-O-Me for RNA).

How to Choose a Service Provider: Key Questions to Ask

1. Experience: Have they developed aptamers for targets similar to your “X”? Ask for case studies or publications.

2. Technology: What is their primary SELEX platform (beads, CE, microfluidic)? Does it suit your target?

3. Characterization: What binding assays do they use to determine Kd? Is it a quantitative, label-free method (SPR, BLI)?

4. Modifications: Can they provide stabilized RNA aptamers (with 2′-F, 2′-NH2) or DNA aptamers? What labeling options do they offer?

5. Timeline & Cost: A full campaign from screening to characterization typically takes 3-6 months and can cost $30,000 – $80,000+, depending on complexity.

6. Intellectual Property (IP): Who owns the resulting aptamer sequences? This is critical. Terms can range from full client ownership to shared or provider-owned IP with licensing.

Leading Companies & Institutions in the Field

• Aptamer Group (UK): One of the most well-known commercial providers.

• Aptagen, LLC (US): Offers custom aptamer development.

• Base Pair Biotechnologies (US): Custom SELEX services with various platforms.

• AptaDiscovery (France/S. Korea): Specializes in Cell-SELEX and protein targets.

• AMSBIO (Distributes aptamers from various sources).

• Academic Labs: Many university labs (e.g., at UCSD, UT Austin, Forschungszentrum Jülich) also offer collaborative or fee-for-service SELEX.

In Summary:

When you seek “X-Aptamer Screening Services,” you are looking for a partner to conduct a customized molecular discovery project. Success hinges on a clear definition of your target (“X”), the desired aptamer properties (affinity, specificity, application), and a well-structured agreement with the service provider covering the technical approach, deliverables, timeline, and IP rights.