The ability to differentiate between BCG-ManLam acknowledges the potential of ZXL1 as a future candidate for developing tuberculosis vaccine (Pan et?al., 2014). crucial for developing newer TB vaccine candidates and/or drugs. In this context, aptamers, also known as chemical antibodies, that specifically recognize or inhibit the function of its virulent proteins are being developed (Chen et?al., 2007). The aptamers are reported 30 years ago in 1990 (Tuerk and Gold, 1990; Ellington and Szostak, 1992). Aptamers are single-stranded DNA or RNA oligonucleotides that are capable of binding target molecules with high specificity and affinity. Structurally, they are relatively small biomolecules (ranging from 20 to 60 nucleotides) and mimic antibodies as they specifically bind to their targets. In comparison to antibodies, they have shorter generation time, lower manufacturing cost, higher modifiability, better thermal stability, higher target potential, and most importantly, no batch-to-batch variability. Due to multiple advantages over antibodies, they are being used as diagnostics, biosensors, and targeted therapeutics (Zhang et?al., 2018) and are touted as a replacement for the use of antibodies in ELISA (Toh et?al., EB 47 2015). In this article, we review the discovery of aptamers with special emphasis on how they are useful for diagnosis and CYFIP1 therapeutic purposes against synthesis of aptamers is known as Systematic Evolution of Ligands by Exponential enrichment (SELEX) (Stoltenburg et?al., 2007). Aptamer generation is usually a long and exhaustive process. Conventionally, an oligonucleotide library contains a pool of 50?90 single-stranded random nucleotide sequences bordered by primer binding sites flanking at both ends. The mechanism of aptamer generation involves the following actions: (i) generation of random library of 1014?1016 single stranded oligonucleotides, (ii) incubation of oligonucleotides with its target, (iii) separation of bound oligonucleotides from unbound ones, (iv) selection of specific oligonucleotides, amplification by PCR (DNA aptamers) or RT?PCR (RNA aptamer), and (v) finally characterization of aptamer by sequencing ( Physique?1 ). For the synthesis of RNA aptamer library, single-stranded DNA library having T7 RNA polymerase promoter sequence at 5-region is EB 47 generated. Such single-stranded DNA library is converted to double-stranded DNA, and transcription is performed to generate the desired RNA aptamers. All the actions are repeated till the desired oligonucleotide (or aptamer) with high binding affinity is usually obtained. Once the desired EB 47 clones are obtained, they are further optimized to maximize the function. They are truncated or reduced in size to achieve minimal aptamer length with maximum binding affinity for the target. The preferred optimal length for aptamers is usually 15?45 nucleotides with molecular weight of 5?15 kDa. Aptamers bind to their targets with pico to micromolar binding affinity. In recent times, various types of SELEX processes have been developed for specific purposes ( Table?1 ). SELEX process-generated aptamers are non-modified, and they are further subjected to various modifications at sugar moiety, phosphate modifications, nucleoside modification, and capping modifications. Some of the examples of modifications are; 2-fluoro (2-F) ribose, 2-amino (2-NH2) ribose, 2-O-methyl (2-OMe) ribose ( Physique?2 ) (Maier and Levy, 2016). Slow off-rate altered aptamers-(SOMAmers) are new class of aptamers where deoxyribose thymine (dT) bases are replaced by deoxyribose uridine (dU) base at 5 position in the heterocyclic ring in oligonucleotide pool. Several replacements can be made at 5 position to generate a vast range of aptamers with different binding affinity and kinetics properties increasing the possibilities of finding suitable aptamer (Maier and Levy, 2016). Naturally occurring nucleotides are D-oligonucleotide, and they form right-handed helix. Mirror image aptamers (spiegelmers) are L-oligonucleotides, and they form left-handed helix. For?spiegelmer generation, first conventional D-oligonucleotides are selected against mirror-image target. The selected D-oligonucleotides are chemically synthesized in reverse configuration as L-oligonucleotides (.