Aptamer Screening Service-Whole-tissue Section SELEX
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Aptamer Screening Service-Whole-tissue Section SELEX

Date：2026-01-08

What is Whole-tissue Section SELEX?

It’s an advanced Systematic Evolution of Ligands by EXponential enrichment (SELEX) technique where the selection target is not a purified protein or single cell type, but an intact, pathological tissue section (e.g., a slice of a human tumor biopsy on a glass slide).

The core idea is to select DNA or RNA aptamers that bind specifically to the molecular landscape of diseased tissue, while simultaneously negating binding to adjacent healthy tissue from the same patient.

The Standard SELEX vs. Whole-Tissue Section SELEX

Feature Standard SELEX Whole-Tissue Section SELEX
Target Purified protein, single cell type, or simple mixture. Complex, native tissue architecture with millions of molecular targets in their natural context.
Goal Find an aptamer for a known, pre-defined target. Discover aptamers for unknown, disease-specific biomarkers without prior target identification.
Context Target is isolated, may have altered conformation. Targets are in their native state, with intact post-translational modifications, protein complexes, and tissue microenvironments.
Counter-Selection Against a buffer or a simple non-target (e.g., BSA). Against a serial section of adjacent healthy tissue from the same patient, ensuring disease specificity.

Why Is This a Powerful Service?

  1. Target-Agnostic Discovery: You don’t need to know the biomarker in advance. The process “lets the tissue decide” what the best molecular targets are.

  2. Clinical Relevance: Selected aptamers recognize epitopes that are:

    • Actually present and accessible in real human disease tissue.

    • Biologically relevant to the pathology.

    • Specific to the disease state versus normal tissue.

  3. Preservation of Native State: It captures the complexity of the tissue proteome/glycome—including protein-protein interactions, membrane complexes, and glycans—that are often lost in protein purification.

  4. Direct Diagnostic/Therapeutic Potential: Aptamers selected this way are immediately candidates for:

    • Diagnostic stains for pathology (like antibodies in IHC).

    • Targeted drug delivery vehicles.

    • In vivo imaging agents.

Typical Workflow of the Service

A service provider would typically execute the following steps:

1. Project Design & Tissue Procurement:

  • You specify the disease of interest (e.g., pancreatic ductal adenocarcinoma, early-stage Alzheimer’s plaque).

  • The service secures matched pairs of FFPE or frozen tissue: Disease Section and Adjacent Healthy Control Section.

2. Library & Preparation:

  • They use a vast, random single-stranded DNA or RNA library (10^14 – 10^15 unique sequences).

  • Tissue sections are prepared and blocked to minimize non-specific binding.

3. The Iterative Selection (SELEX) Rounds:

  • Positive Selection: The library is incubated on the disease tissue section. Unbound sequences are washed away.

  • Recovery: Bound sequences are eluted (e.g., by heat, proteinase K, or tissue scraping).

  • Negative Counter-Selection: The eluted pool is incubated on the healthy control tissue section. Sequences that bind here are discarded. The unbound pool (now enriched for disease-specific binders) is recovered.

  • Amplification: The recovered pool is amplified by PCR (for DNA) or RT-PCR (for RNA) to create a new library for the next round.

  • This cycle is repeated (8-15 rounds) until a highly enriched pool is obtained.

4. High-Throughput Sequencing & Bioinformatics:

  • The final pool is sequenced (NGS).

  • Bioinformatic analysis identifies sequence families that have converged and enriched over the rounds.

5. Aptamer Characterization & Validation:

  • Individual aptamer candidates are synthesized and tested.

  • Validation: Binding is confirmed on independent tissue sets (a tissue microarray – TMA is ideal) to verify specificity and sensitivity.

  • Target Identification (Optional but critical): Using the aptamer as a “hook” to pull down and identify its target protein via mass spectrometry. This is where the unknown biomarker is revealed.

Key Advantages and Challenges of the Service

Advantages for the Client:

  • Access to a complex, proprietary technology without needing in-house SELEX expertise.

  • Receipt of fully validated, tissue-specific aptamers and, potentially, the identification of a novel biomarker.

  • Accelerated path from discovery to diagnostic/therapeutic application.

Technical Challenges the Service Must Overcome:

  • High Complexity: Managing background binding to tissue components (e.g., collagen, extracellular matrix).

  • Target Identification: This is the most difficult, non-trivial step. The target may be a rare protein, a specific glycoform, or a complex.

  • Cost & Time: It’s more expensive and time-consuming than conventional SELEX due to the use of precious tissue samples and complex analysis.

Who Uses This Service?

  • Pharma/Biotech: For discovering novel targets and developing targeted therapeutics/diagnostics.

  • Academic Researchers: In cancer, neurology, cardiovascular disease—any field where tissue-specific biomarkers are needed.

  • Diagnostic Companies: To develop next-generation, aptamer-based in-situ diagnostic assays.

In Summary

Aptamer Screening via Whole-tissue Section SELEX is a premier, discovery-focused service. It moves beyond the “one target, one aptamer” paradigm to a systems biology approach, mining the actual molecular signature of disease. The output is not just a binding molecule, but a specific probe for a pathologically relevant epitope and a potential roadmap to a new biomarker.

When evaluating such a service, key questions to ask the provider are: their experience with your specific tissue type, their strategy for counter-selection and managing background, their process for target identification, and examples of past successes with validation on TMAs.