Advances in Aptamer-Based Biomarker Discovery

Abstract

The discovery and identification of biomarkers promote the rational and fast development of medical diagnosis and therapeutics. Clinically, the application of ideal biomarkers still is limited due to the suboptimal technology in biomarker discovery. Aptamers are single-stranded deoxyribonucleic acid or ribonucleic acid molecules and can selectively bind to varied targets with high affinity and specificity. Compared with antibody, aptamers have desirable advantages, such as flexible design, easy synthesis and convenient modification with different functional groups. Currently, different aptamer-based technologies have been developed to facilitate biomarker discovery, especially CELL-SELEX and SOMAScan technology. CELL-SELEX technology is mainly used to identify cell membrane surface biomarkers of various cells. SOMAScan technology is an unbiased biomarker detection method that can analyze numerous and even thousands of proteins in complex biological samples at the same time. It has now become a large-scale multi-protein biomarker discovery platform. In this review, we introduce the aptamer-based biomarker discovery technologies, and summarize and highlight the discovered emerging biomarkers recently in several diseases.

Keywords: CELL-SELEX; SOMAScan; aptamer; biomarker discovery; human diseases.

FIGURE 1

Schematic representation of CELL-SELEX. The process involves repeated cycles of: (1) Target cells are firstly incubated with the initial oligonucleotide library for positive selection; (2) Bound oligonucleotides are incubated with negative cells for negative selection, then unbound oligonucleotides were amplified to generate a new library of oligonucleotides for the next selection round. After about 20 cycles, several aptamers can be selected. Finally, Candidate aptamers are selected by cloning and sequencing the aptamer pool.

FIGURE 2

Schematic representation of SOMAScan. (1) SOMAmers are mixed with the target sample forming SOMAmer-protein complexes. These complexes are tagged with biotin (B) and fluorescent label (F). (2) These complexes are captured onto avidin bead (AB) with streptavidin (SA). (3) The captured proteins were labeled with biotin. (4) The complexes were released from beads through ultraviolet light (hv). (5) Polyanionic competitors (PC) were added to promote the dissociation between proteins and non-specific SOMAmers. (6) Bound complexes are captured onto primer beads (PB). (7) Captured complexes are dissociated with 20 mM NaOH.