Biomarkers are signature molecules that can indicate specific physiological states of cells. Identification of reliable biomarkers is important for early diagnosis and adaptive treatment of diseases. Diagnostic aptamers, therapeutic aptamers aptamers as well as aptamers in biomarker discovery have shown promise. Using complex samples as targets and improved SELEX methods, a panel of aptamers can be systematically generated by Creative Biolabs for comprehensive recognition of biomarkers. Based on years of professional experience, Creative Biolabs is competent to provide high-quality aptamer-based biomarker discovery services for global researchers.
The discovery and identification of biomarkers promote the rational and fast development of medical diagnosis and therapeutics. Conventional approaches for biomarker discovery mainly involve genomics and proteomics. However, gene expression does not always correlate with the abundance and the variation of encoded proteins, which are often subject to post-translational modification (PTM) or proteolytic cleavage. Proteomic methods, which focus on characterizing the expression and alteration of proteins, are more straightforward for interpreting the cellular phenotype. By combining mass spectrometry (MS) with two-dimensional gel electrophoresis (2D-GE), some progress has been made in proteome analysis and specific protein identification. However, these technologies tend to provide false-positive results originating from intensive sample processing, including cell/tissue lysis, isolation, and purification.
Fig.1 Techniques used for biomarker identification and detection. (Altintas, 2015)
Another classical method for biomarker discovery has been the incorporation of antibodies. Antibody-based strategies often require a sandwich system for screening target proteins. This means that two antibodies must be able to properly identify the target, making large-scale biomarker screening impractical under these conditions. Moreover, the systematic production of antibody libraries for molecular differentiation of cancer cells is very difficult.
At present, different aptamer-based screening technologies have been developed to facilitate biomarker discovery. SOMAS can technology is an unbiased biomarker detection method that can analyze numerous and even thousands of proteins in complex biological samples at the same time. Cell-SELEX technology is mainly used to identify cell membrane surface biomarkers of various cells.
A promising detection platform that can quantify the expression levels of a variety of proteins will deliver valuable information concerning disease diagnosis. Aptamers can distinguish among thousands of proteins and do so in a short period, and they can detect small differences between proteins that are quite similar in structure. Multiplexed systems that incorporate aptamers for a variety of proteins can be performed, and the aptamers that do bind to protein can be quantified via microarray analysis to determine the ratio of specific proteins.
Fig.2 Schematic representation of Cell-SELEX (A) and SOMAScan (B). (Huang, 2021)
Aptamer-based biomarkers discovery broadens the road and increases the sensitivity to explore novel biomarkers. Aptamers can not only provide a way of discovering biomarkers that help to differentiate between normal cells and cancer cells, but they can also help to differentiate the stage of carcinogenesis within one subtype of cancer. Besides, it is worth noting that single biomarkers are difficult to diagnose disease and clarify mechanisms. Thus, biomarker panels should be highly suggested and combining with clinical indicators to improve the predictive power of diseases.
Traditional biomarker discovery is a long process and relies on multiple comparisons using various analytical techniques. The unique process of advanced aptamer selection offers exciting opportunities for biomarker discovery, while aptamer selectivity and stability make them ideal reagents for biomarker assay development. Cell-SELEX is an exciting technique that enables the selection of aptamers without prior identification of a specific cell surface target. The selection of aptamer affinity reagents to cells or unknown targets of interest is used to identify new disease-specific targets for therapeutic development and early-stage diagnostics. Combining traditional SELEX with cell-SELEX helps ensure selectivity for cell surface targets in their native form.
Creative Biolabs has performed several cell-SELEX projects, including the selection of aptamers to cell-surface markers and the identification of aptamers that enter specific cells. If you are interested in our biomarker discovery services, please feel free to contact us for more information.
References
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