Abstract
Tuberculosis (TB) has been plaguing human civilization for centuries, and currently around one-third of the global population is affected with TB. Development of novel intervention tools for early diagnosis and therapeutics against Mycobacterium tuberculosis (M.tb) is the main thrust area in today’s scenario. In this direction global efforts were made to use aptamers, the chemical antibodies as tool for TB diagnostics and therapeutics. This review describes the various aptamers introduced for targeting M.tb and highlights the need for development of novel aptamers to selectively target virulent proteins of M.tb for vaccine and anti-TB drugs. The objective of this review is to highlight the diagnostic and therapeutic application of aptamers used for tuberculosis. The discovery of aptamers, SELEX technology, different types of SELEX development processes, DNA and RNA aptamers reported for diseases and pathogenic agents as well have also been described in detail. But the emphasis of this review is on the development of aptamers which can block the function of virulent mycobacterial components for developing newer TB vaccine candidates and/or drug targets. Aptamers designed to target M.tb cell wall proteins, virulent factors, secretory proteins, or combination could orchestrate advanced diagnosis and therapeutic measures for tuberculosis.
Highlights
Tuberculosis (TB) caused by Mycobacterium tuberculosis (M.tb) is a leading cause of death from a single infectious agent worldwide
Our current knowledge of cellular and molecular interactions between mycobacteria and host immune responses is poor, and the complex pathobiology of tuberculosis presents a significant challenge in vaccine development
Aptamers which can detect early infection stages or detect drug-resistant M.tb strain would be effective in the management of TB
Summary
Tuberculosis (TB) caused by Mycobacterium tuberculosis (M.tb) is a leading cause of death from a single infectious agent worldwide. Aptamers are single-stranded DNA or RNA oligonucleotides that are capable of binding target molecules with high specificity and affinity. The mechanism of aptamer generation involves the following steps: (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) characterization of aptamer by sequencing (Figure 1). Aptamers are either further developed for several applications like therapeutics and diagnostics (successful) or again feed into the same SELEX cycle (unsuccessful) In this method, well- characterized aptamers are fused together so that the resulting aptamer Burke and Willis, 1998 can bind to different targets (one aptamer can recognise two or more different targets). Nucleotides are light-sensitive and irradiation with UV rays is employed to Golden et al, 2000 select the specific aptamer-target from the pool
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