Core Technology: SELEX The foundation of all these services is the SELEX process, an in vitro method to select aptamers from a vast random library (typically 10^13 - 10^15 unique sequences). The library is incubated with the target, unbound sequences are washed away, and bound sequences are eluted and amplified by PCR (for DNA) or RT-PCR (for RNA). This cycle is repeated 8-15 times to enrich for the tightest binders. Services for Protein Targets This is the most common application, as aptamers are often touted as "chemical antibodies." 1. Standard Protein SELEX: Target: Purified, recombinant proteins (e.g., cytokines, receptors, enzymes, viral capsids). Key Considerations: Protein Purity & Conformation: Critical for success. Services often require >90% purity and verification of native folding. Immobilization: The protein is usually immobilized on beads (e.g., streptavidin/biotin, Ni-NTA/His-tag) to facilitate partitioning. Some services offer solution-phase SELEX to avoid conformation changes. Counter-Selection: To ensure specificity, libraries are pre-incubated with related proteins or the immobilization matrix to subtract non-specific binders. 2. Specialized SELEX for Complex Proteins: Membrane Protein SELEX: For receptors and channels. Requires special handling (e.g., use of nanodiscs, detergent micelles, or whole cells overexpressing the target). Post-Translationally Modified Protein SELEX: For targets where phosphorylation, glycosylation, etc., are essential for function. 3. Cell-SELEX (for Cell-Surface…
What is CE-SELEX? SELEX (Systematic Evolution of Ligands by EXponential Enrichment) is the standard process for aptamer development. It involves iterative rounds of selection and amplification to enrich nucleic acid sequences that bind tightly to a target molecule. Traditional SELEX often uses immobilization of the target on beads or filters, which can be slow (8-15 rounds) and may introduce bias by selecting for sequences that bind to the immobilization matrix itself. CE-SELEX uses Capillary Electrophoresis as the separation mechanism. The key principle is that when an aptamer binds to its target, it forms a complex with a different charge-to-size ratio, causing it to migrate at a different time (shifted peak) in the capillary compared to the unbound nucleic acid library. This complex can be isolated and collected with exquisite precision. Core Advantages of a CE-SELEX Screening Service A service provider offering CE-SELEX delivers significant benefits: Extreme Speed and Efficiency: Often requires only 2-4 rounds of selection to obtain high-affinity aptamers (nanomolar to picomolar Kd), compared to many more rounds in traditional SELEX. This translates to weeks or months of time saved. Solution-Phase Selection: The target is free in solution, eliminating immobilization bias. This allows for selection against targets in their native conformation and enables selection for small molecules and…
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: Library Design & Synthesis: Creating the initial random oligonucleotide pool. Incubation: The library is exposed to the target. Partitioning: Bound sequences are separated from unbound ones (the most critical step, varying by target type). Amplification: The bound sequences are amplified (usually by PCR for DNA, RT-PCR for RNA). 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. Repetition: Steps 2-5 are repeated for 8-15 rounds until a high-affinity pool is enriched. Cloning & Sequencing: The final pool is cloned, and individual aptamer sequences are identified via Next-Generation Sequencing (NGS). Bioinformatics & Analysis: NGS data is analyzed to identify candidate sequences, often clustered into families based on sequence/structure motifs. Characterization: Top candidates…
Aptamers are single-stranded oligonucleotides that fold into defined architectures and bind to targets such as proteins. In binding proteins they often inhibit protein–protein interactions and thereby may elicit therapeutic effects such as antagonism. Aptamers are discovered using SELEX (systematic evolution of ligands by exponential enrichment), a directed in vitro evolution technique in which large libraries of degenerate oligonucleotides are iteratively and alternately partitioned for target binding. They are then amplified enzymatically until functional sequences are identified by the sequencing of cloned individuals. For most therapeutic purposes, aptamers are truncated to reduce synthesis costs, modified at the sugars and capped at their termini to increase nuclease resistance, and conjugated to polyethylene glycol or another entity to reduce renal filtration rates. The first aptamer approved for a therapeutic application was pegaptanib sodium (Macugen; Pfizer/Eyetech), which was approved in 2004 by the US Food and Drug Administration for macular degeneration. Eight other aptamers are currently undergoing clinical evaluation for various haematology, oncology, ocular and inflammatory indications. Aptamers are ultimately chemically synthesized in a readily scalable process in which specific conjugation points are introduced with defined stereochemistry. Unlike some protein therapeutics, aptamers do not elicit antibodies, and because aptamers generally contain sugars modified at their 2′-positions,…
What is an Aptamer? An aptamer is a short, single-stranded oligonucleotide (DNA or RNA) or peptide that binds to a specific target molecule (e.g., proteins, small molecules, cells, viruses) with high affinity and specificity. Often called "chemical antibodies," they offer advantages like stability, low-cost synthesis, and minimal batch-to-batch variation. The Core Process: SELEX The standard method for aptamer selection is SELEX (Systematic Evolution of Ligands by EXponential enrichment). Basic SELEX Workflow: Library Synthesis: Create a vast random-sequence oligonucleotide library (typically 10¹³ - 10¹⁵ unique sequences) flanked by constant primer regions for PCR amplification. Incubation: The library is incubated with the target molecule under controlled conditions (buffer, temperature, time). Partitioning: Bound sequences are separated from unbound ones. This is the most critical step and varies based on target (e.g., filtration, affinity columns, magnetic bead separation). Elution: Bound aptamers are recovered from the target (e.g., by denaturation or competitive elution). Amplification: The recovered pool is amplified by PCR (for DNA) or RT-PCR (for RNA) to create an enriched library for the next round. Iteration: Steps 2-5 are repeated (typically 8-15 rounds) to progressively enrich for sequences with the highest affinity and specificity. Cloning & Sequencing: The final enriched pool is cloned and sequenced to identify individual aptamer candidates. Key Variants of…
Small molecules are some of the most valuable—and most difficult—targets in molecular recognition. They include metabolites, drugs, toxins, cofactors, and signaling compounds that often weigh only a few hundred Daltons. Developing expertise in aptamers to small molecules means mastering a set of selection and validation strategies that differ substantially from protein-target aptamer work, because small molecules offer fewer contact points, weaker “handles” for separation, and more ways to generate false positives. This article explains how small-molecule aptamers are discovered, why selection is uniquely challenging, how advanced SELEX variants improve success rates, and what “good” looks like when you engineer an aptamer into a sensor, assay, or therapeutic concept. 1) What makes small-molecule aptamers special? Aptamers are single-stranded DNA or RNA sequences that fold into 3D shapes able to bind a target through non-covalent interactions—hydrogen bonding, π–π stacking, electrostatics, and shape complementarity. For proteins, large surfaces provide many contacts, so binding can be robust even when the selection workflow is imperfect. Small molecules are different: Tiny binding interface: fewer interaction opportunities means affinity can be harder to evolve and easier to mis-measure. Separation is tricky: in classic SELEX you often immobilize the target; immobilization can change the target’s presentation…
Aptamers are short single-stranded DNA or RNA molecules that fold into 3D structures capable of binding targets (proteins, small molecules, cells, or even complex particles) with high specificity and affinity. “Aptamer methods” usually refers to the full pipeline: library design → selection (SELEX) → enrichment monitoring → sequencing & bioinformatics → candidate optimization → biophysical/functional validation → stability engineering. Modern platforms improve speed and hit quality by combining smarter selection pressures with microfluidics and next-generation sequencing. 1) Core Aptamer Selection Method: SELEX (Systematic Evolution of Ligands by EXponential Enrichment) 1.1 Classical SELEX workflow (baseline method) Start with a random oligonucleotide library (often 10^13–10^15 unique sequences) Incubate library with the target Partition bound vs unbound sequences Elute binders Amplify (PCR for DNA; RT-PCR + transcription for RNA) Repeat iterative rounds with increasing stringency until enrichment is achieved Why it works: each round increases the fraction of sequences that can bind under the imposed conditions (buffer, temperature, competitor molecules, etc.). Why it’s hard: classical SELEX can be slow, labor intensive, and prone to amplification bias—hence the rise of “advanced SELEX” platforms. 1.2 “Stringency engineering” (how you make aptamers useful) Selection success often depends less on the target itself…
CUSTOM APTAMER DISCOVERY & DEVELOPMENT is the process of creating target-specific single-stranded DNA or RNA aptamers—short nucleic acids that fold into 3D shapes capable of binding proteins, small molecules, cells, vesicles, or other targets with antibody-like selectivity. Most custom programs rely on SELEX (Systematic Evolution of Ligands by EXponential enrichment), then refine “hits” into robust, application-ready binders through sequencing-driven analysis and post-selection optimization. 1) What Aptamers Are (and Why They’re Used) Aptamers are typically ~15–90 nucleotides long and can be engineered to bind targets across a wide size range (from small molecules to whole cells). They’re attractive because they are chemically synthesized (batch-to-batch consistency), can be readily labeled (fluorophores, biotin, etc.), and are generally thermally stable and re-foldable—features that often simplify assay development and manufacturing. Common aptamer use cases Diagnostics & biosensors (capture probes, signal transducers, point-of-care formats) Targeted delivery & therapeutics research (cell-directed binding, payload delivery concepts) Affinity purification & analytical workflows (pull-downs, enrichment, separations) 2) The Core Workflow in Custom Aptamer Discovery A custom program is best thought of as a pipeline with four linked decisions: target format → selection strategy → analytics → optimization. Step A — Target Definition and “Bindability” Planning…
Aptamers are short, single-stranded nucleic acid molecules (DNA or RNA) that fold into specific 3D shapes and bind targets with high affinity and selectivity—often compared to how antibodies recognize antigens, but built from nucleic acids rather than proteins. Unlike a “generic DNA strand,” an aptamer’s function comes from structure: loops, stems, bulges, pseudoknots, and other motifs that create a binding surface matching a target’s geometry and chemistry. Targets can include proteins, peptides, small molecules, ions, and even whole cells (depending on the selection strategy). Why Aptamers Matter (and How They Differ From Antibodies) Aptamers are often described as “chemical antibodies,” but the differences are exactly why they’re valuable. Key advantages frequently highlighted Low immunogenicity (reduced risk of provoking immune responses) High stability and the ability to refold after denaturation in many cases Easy chemical synthesis (batch consistency, scalable manufacturing) Straightforward modification (labels, linkers, immobilization handles) Trade-offs you should know Nuclease sensitivity (especially RNA aptamers) can be a limitation in biological fluids unless stabilized. Selection bias can occur during discovery (e.g., PCR bias), meaning “best in the tube” isn’t always “best in reality.” Very high affinity does not automatically guarantee best real-world specificity; selection conditions matter. …
