Aptamers, often referred to as "chemical antibodies", are single-stranded oligonucleotides (DNA or RNA) that fold into highly specific three-dimensional structures, enabling them to bind to a vast array of target molecules with high affinity. This molecular recognition capability positions them as superior affinity reagents for research, diagnostics, and therapeutics. At CD BioGlyco, we leverage expertise in biological synthesis and screening to offer a cutting-edge aptamer synthesis service, designed to deliver robust, high-performance ligands tailored precisely to your project's unique requirements. Our commitment to chemical synthesis ensures unparalleled consistency, scalability, and quality, eliminating the batch-to-batch variability often associated with traditional biological recognition molecules.
Our customized platform is engineered for high stringency and efficiency. It utilizes a vast combinatorial library of single-stranded nucleic acids, typically containing millions to billions of different sequences, ensuring comprehensive coverage of potential binding structures. We employ state-of-the-art partitioning methods, including magnetic bead separation, capillary electrophoresis, and bead-based flow cytometry, allowing for the precise isolation and enrichment of target-bound sequences under conditions that mimic the intended final application environment (e.g., biological fluids or cellular matrix).
A critical aspect of our core technology is the integration of chemically modified nucleotides during the selection and synthesis phases. While native RNA is prone to rapid degradation by nucleases, CD BioGlyco routinely employs modifications like 2'-fluoro and 2'-amino substitutions to the sugar backbone. These modifications significantly enhance nuclease resistance and stability, making the resulting aptamers functional for in vivo and harsh diagnostic applications. Chemical synthesis ensures precise placement of these modifications, leading to highly stable and robust ligands that can tolerate a broad range of pH and temperature conditions, greatly extending shelf life and ease of transport compared to antibodies.
CD BioGlyco is equipped to handle a comprehensive range of client requirements across various target types and end-use applications:
Selection against virtually any target, including proteins (recombinant, native, modified), peptides, small molecules, heavy metals, toxins, carbohydrates, viruses, bacteria, and whole cells (e.g., cancer cell lines).
Specialized methodologies for non-immunogenic or toxic targets, which are often intractable with antibody development, are achieved by using non-biological, in vitro selection methods.
Development of either DNA aptamers (generally higher stability and lower synthesis cost for diagnostics) or RNA aptamers (often providing higher structural diversity, suitable for riboswitch or specific therapeutic applications).
Seamless integration of non-natural bases and chemical modifications to enhance resistance to nucleases and customize pharmacokinetic properties for in vivo use.
Screening for non-overlapping binding pairs for "sandwich" assay formats (e.g., ELISA/ALISA) or creating multivalent aptamer constructs (e.g., conjugated to nanoparticles) to boost avidity and targeting efficiency.
Comprehensive binding kinetics, thermal stability, and structure analysis to provide complete data packages necessary for regulatory filings and subsequent development stages.
We initiate the process by comprehensively analyzing the client’s target molecule (protein, small molecule, cell, etc.). Based on this, we design the optimal random oligonucleotide library, selecting the appropriate nucleic acid type (DNA, RNA, or modified XNA).
A massive random oligonucleotide library is chemically synthesized with high purity. This step is crucial for ensuring the diversity required to find the highest affinity binders during selection.
The synthesized library is incubated with the immobilized or suspended target. Unbound sequences are washed away, and high-affinity binders are eluted. These binders are then amplified via PCR (with reverse transcription for RNA aptamers) to create the enriched pool for the next round. Conditions are continually optimized across cycles to increase stringency.
In parallel rounds, the enriched library is screened against non-target molecules or control cells to ensure the resulting aptamers are highly specific and do not bind to closely related non-target components, a step critical for in vivo applications.
The enriched pools are subjected to next-generation sequencing (NGS) to identify the most abundant, high-frequency candidate sequences. Advanced proprietary algorithms are then used to predict secondary and tertiary structures, identify consensus motifs, and rank candidates based on enrichment rate.
The top-ranked sequences are individually synthesized in large, purified quantities. Comprehensive characterization (e.g., ELISA, SPR, or MST) is performed to confirm binding affinity and specificity against the target, providing the client with definitive performance data.
Journal: Pharmaceuticals
DOI: 10.3390/ph18121867
IF: 4.8
Published: 2025
Results: This study designed and synthesized a novel class of aptamer conjugates (APCs) by chemically linking the nucleolin (NCL)-targeting DNA aptamer to the E3 ubiquitin ligase ligand lenalidomide. Among the synthesized chimeras (C1-C4), C4 was identified as the most potent compound, demonstrating superior ability to inhibit the proliferation of MCF-7 breast cancer cells and significantly downregulate NCL protein levels in a dose- and time-dependent manner. Mechanistic investigations confirmed that C4 induces NCL degradation via the ubiquitin-proteasome pathway by facilitating the formation of a ternary complex between NCL and the CRBN E3 ligase. Furthermore, C4 promoted apoptosis and cell cycle arrest in cancer cells while retaining the cancer cell-specific targeting of the original AS1411 aptamer. In vivo experiments using a mouse xenograft model showed that C4 potently suppressed tumor growth without inducing observable systemic toxicity. The research validates the APC strategy as a promising approach for targeted protein degradation and identifies C4 as a highly promising candidate for anticancer therapy.
Molecular Diagnostics and Biosensors
Aptamers serve as highly sensitive biorecognition elements in advanced biosensor platforms, lateral flow assays, and plate-based assays (ELISA-like formats, known as ELASA or ALISA). Their stability and ease of functionalization allow for high-density immobilization, leading to reusable and highly sensitive diagnostic tools for early disease detection and environmental monitoring.
Targeted Drug Delivery Systems
Aptamers can be conjugated to small molecule drugs, chemotherapy agents, or nanoparticles (NP-aptamer bioconjugates) to create highly selective delivery vehicles. The aptamer guides the therapeutic payload specifically to cells or tissues overexpressing a target biomarker, such as cancer cells, minimizing off-target toxicity and improving therapeutic index.
Therapeutic Intervention (Aptamer Drugs)
Aptamers can act directly as therapeutic agents by binding to and inhibiting the function of key proteins (e.g., growth factors, receptors, enzymes) involved in disease pathways. They can also act as agonists, regulating cellular processes by inducing conformational changes in their targets, offering a novel class of precision medicine.
Flow Cytometry and Cell Sorting
Used as superior alternatives to antibodies for labeling and separating specific cell populations. Their small size and synthetic purity allow for highly consistent staining and sorting, and their chemical synthesis enables production suitable for handling potentially therapeutic cell lines.
Superior Batch-to-Batch Uniformity and Scalability
Unlike antibodies, which rely on biological cell culture systems and often suffer from inherent batch variability, aptamers are produced entirely through chemical synthesis. This process is highly controlled, reproducible, sequence-independent, and easily scaled up to deliver highly pure, homogeneous reagents from milligram to multi-gram quantities with minimal variation.
Exceptional Thermal and Chemical Stability
Aptamers can be reversibly denatured and refolded without loss of function and exhibit stability across a broad range of pH and temperatures (including lyophilized storage at room temperature), significantly simplifying logistics, storage, and application in harsh environmental conditions compared to temperature-sensitive antibodies.
Engineered In Vivo Performance
Through the incorporation of advanced chemical modifications (like 2'-fluoro or PEGylation), we create nuclease-resistant aptamers with finely tuned half-lives, mitigating the common bottlenecks of degradation and rapid renal filtration observed with unmodified oligonucleotides.
Low to Zero Immunogenicity
Being composed of nucleic acids (oligos) and selected in vitro, aptamers elicit little or no adverse immune response, making them ideal candidates for therapeutic applications where repeated dosing is necessary and immunotoxicity is a major concern.
We required a highly stable, chemically modified aptamer for an in vivo imaging project. CD BioGlyco not only delivered the aptamer but also integrated the required fluorophore with flawless purity. The stability of the final product in serum was exactly as promised, enabling successful in vivo targeting.
— Research Associate, Translational Medicine Department
The customer service and scientific consultation were exceptional. They guided us on the optimal target preparation method, which was key to the project's success. The final aptamer has exceptional stability and has performed perfectly in our lateral flow immunoassay.
— Manager, Head of Product Development, Medical Devices Group
The team delivered an aptamer targeting a complex GPCR that our antibody vendor couldn't touch. The specificity and affinity they achieved were outstanding, and the data were impeccably detailed.
— Dr. Chen, Senior Principal Scientist, Oncology Division
To help you achieve your goals related to your newly synthesized aptamer, we offer a comprehensive suite of complementary molecular biology and oligonucleotide services. These services are often critical for downstream development, especially if your aptamer is an RNA sequence or is intended for functional in vitro transcription/translation applications.
If your final application involves expressing a nucleic acid in a cell, our expert team can optimize the sequence of your aptamer (or a therapeutic sequence derived from it) for stability, translation efficiency, and reduced immunogenicity in specific cellular environments.
High-purity linear or plasmid DNA templates are essential for scale-up synthesis or for subsequent in vitro transcription of RNA aptamers. We provide reliable, high-yield preparation services tailored to the specific needs of your aptamer sequence.
Beyond the basic aptamer modifications, we offer specialized modification services, including the incorporation of pseudouridine and other non-standard nucleosides, crucial for enhancing the stability and translational efficiency of mRNA-based therapeutics or related constructs.
We provide rigorous purification methods, including HPLC and PAGE, to ensure the final product—whether the aptamer itself or an associated mRNA transcript—meets the highest standards of purity for your research or clinical use.
At CD BioGlyco, our aptamer synthesis service provides you with a robust and highly specific alternative to traditional antibodies. We offer synthetic flexibility, chemical stability, and customizable IP to ensure your transition from discovery to application is seamless and successful. Trust our expertise to deliver the precision ligands required for your next generation of diagnostics, therapeutics, or fundamental research tools. Contact us!
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