Identification and Engineering of Aptamers for Theranostic Application in Human Health and Disorders

Aptamer is short sequence of synthetic oligonucleotides which bind to their cognate target specifically while maintaining similar or higher sensitivity as antibody. Small size, chemical synthesis, low batch variation, cost effectiveness, long shelf life and above all low immunogenicity provide advantages over antibody. The in-vitro selection of aptamer applying a conjoining approach of chemistry and molecular biology is referred as Systematic Evolution of Ligands by Exponential enrichment (SELEX). These initial products of SELEX are considered as first generation aptamers, further modified chemically in an attempt to make it stable in biofluid avoiding nuclease digestion and renal clearance. These types of aptamers are called second generation aptamers. While modification is incorporated, enough care should be taken to maintain its sensitivity and specificity. These modifications and several improvisations have widened the window frame of aptamer application that is currently not only restricted to in-vitro system, but have been used in molecular imaging for disease pathology and treatment. In food industry it is used as sensor for detection of different diseases or fungal infections. In this review we have discussed a brief history of its journey, process of synthesis, different types of modifications to improve its characters. We have also focused on its applications and highlighted its role as therapeutic plus diagnostic; theranostic tools. Finally, the review is concluded with a brief discussion on future prospective in immunotherapy, as well as in identification of novel biomarkers in stem cell, and also in single cell proteomics (scProteomics) to study intra or intertumor heterogeneity at protein level.

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Identification and Engineering of Aptamers for Theranostic Application in Human Health and Disorders

International Journal of Molecular Sciences ◽

10.3390/ijms22189661 ◽

2021 ◽

Vol 22 (18) ◽

pp. 9661

Author(s):

Debleena Basu ◽

Sourabrata Chakraborty ◽

Riddhi Pal ◽

Tarun Kumar Sharma ◽

Siddik Sarkar

Keyword(s):

Human Health ◽

In Vitro Selection ◽

Fungal Infections ◽

Chemical Properties ◽

Nuclease Digestion ◽

History Of ◽

In Vitro Systems ◽

Novel Biomarkers ◽

Physical And Chemical

An aptamer is a short sequence of synthetic oligonucleotides which bind to their cognate target, specifically while maintaining similar or higher sensitivity compared to an antibody. The in-vitro selection of an aptamer, applying a conjoining approach of chemistry and molecular biology, is referred as Systematic Evolution of Ligands by Exponential enrichment (SELEX). These initial products of SELEX are further modified chemically in an attempt to make them stable in biofluid, avoiding nuclease digestion and renal clearance. While the modification is incorporated, enough care should be taken to maintain its sensitivity and specificity. These modifications and several improvisations have widened the window frame of aptamer applications that are currently not only restricted to in-vitro systems, but have also been used in molecular imaging for disease pathology and treatment. In the food industry, it has been used as sensor for detection of different diseases and fungal infections. In this review, we have discussed a brief history of its journey, along with applications where its role as a therapeutic plus diagnostic (theranostic) tool has been demonstrated. We have also highlighted the potential aptamer-mediated strategies for molecular targeting of COVID-19. Finally, the review focused on its future prospective in immunotherapy, as well as in identification of novel biomarkers in stem cells and also in single cell proteomics (scProteomics) to study intra or inter-tumor heterogeneity at the protein level. Small size, chemical synthesis, low batch variation, cost effectiveness, long shelf life and low immunogenicity provide advantages to the aptamer over the antibody. These physical and chemical properties of aptamers render them as a strong biomedical tool for theranostic purposes over the existing ones. The significance of aptamers in human health was the key finding of this review.

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In vitro selection of tacrolimus binding aptamer by systematic evolution of ligands by exponential enrichment method for the development of a fluorescent aptasensor for sensitive detection of tacrolimus

Journal of Pharmaceutical and Biomedical Analysis ◽

10.1016/j.jpba.2019.112853 ◽

2020 ◽

Vol 177 ◽

pp. 112853 ◽

Cited By ~ 1

Author(s):

Atena Mansouri ◽

Khalil Abnous ◽

Maryam Sadat Nabavinia ◽

Mohammad Ramezani ◽

Seyed Mohammad Taghdisi

Keyword(s):

In Vitro Selection ◽

Sensitive Detection ◽

Enrichment Method ◽

Systematic Evolution ◽

Exponential Enrichment ◽

Selection Of ◽

Fluorescent Aptasensor

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In vitro selection of an RNA aptamer yields an interleukin-6/interleukin-6 receptor interaction inhibitor

Bioscience Biotechnology and Biochemistry ◽

10.1093/bbb/zbaa124 ◽

2021 ◽

Author(s):

Takehiro Ando ◽

Mizuki Yamamoto ◽

Yukio Takamori ◽

Keita Tsukamoto ◽

Daisuke Fuji ◽

...

Keyword(s):

Interleukin 6 ◽

In Vitro Selection ◽

Receptor Interaction ◽

Rna Aptamer ◽

Cytokine Storm ◽

Interleukin 6 Receptor ◽

Systematic Evolution ◽

Exponential Enrichment ◽

Selection Of

ABSTRACT Interleukin-6 (IL-6) binds to IL-6 receptor (IL-6R) subunit, related to autoimmune diseases and cytokine storm in COVID-19. In this study we performed Systematic Evolution of Ligands by Exponential enrichment (SELEX) and identified a novel RNA aptamer. This RNA aptamer not only bound to IL-6R with a dissociation constant of 200 nM, but also inhibited the interaction of IL-6R with IL-6.

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Faculty Opinions recommendation of In vitro selection of a deoxyribozyme that can utilize multiple substrates.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1004319.49956 ◽

2002 ◽

Author(s):

Niles Lehman

Keyword(s):

In Vitro Selection ◽

Multiple Substrates ◽

Selection Of

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Faculty Opinions recommendation of CIS display: In vitro selection of peptides from libraries of protein-DNA complexes.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1017658.206556 ◽

2004 ◽

Author(s):

Sachdev Sidhu

Keyword(s):

In Vitro Selection ◽

Dna Complexes ◽

Selection Of

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The Effects of Shock Vancomycin Concentrations on the Formation of Heteroresistance in Staphylococcus aureus

Antibiotics and Chemotherapy ◽

10.37489/0235-2990-2020-65-9-10-3-7 ◽

2020 ◽

Vol 65 (9-10) ◽

pp. 3-7

Author(s):

V. V. Gostev ◽

Yu. V. Sopova ◽

O. S. Kalinogorskaya ◽

M. E. Velizhanina ◽

I. V. Lazareva ◽

...

Keyword(s):

Staphylococcus Aureus ◽

In Vitro Selection ◽

Methicillin Resistant Staphylococcus Aureus ◽

High Concentration ◽

Short Term ◽

High Concentrations ◽

Selection Of ◽

Selection Of Resistance ◽

Test Cultures

Glycopeptides are the basis of the treatment of infections caused by MRSA (Methicillin-Resistant Staphylococcus aureus). Previously, it was demonstrated that antibiotic tolerant phenotypes are formed during selection of resistance under the influence of high concentrations of antibiotics. The present study uses a similar in vitro selection model with vancomycin. Clinical isolates of MRSA belonging to genetic lines ST8 and ST239, as well as the MSSA (ATCC29213) strain, were included in the experiment. Test isolates were incubated for five hours in a medium with a high concentration of vancomycin (50 μg/ml). Test cultures were grown on the medium without antibiotic for 18 hours after each exposure. A total of ten exposure cycles were performed. Vancomycin was characterized by bacteriostatic action; the proportion of surviving cells after exposure was 70–100%. After selection, there was a slight increase in the MIC to vancomycin (MIC 2 μg/ml), teicoplanin (MIC 1.5–3 μg/ml) and daptomycin (MIC 0.25–2 μg/ml). According to the results of PAP analysis, all strains showed an increase in the area under curve depending on the concentration of vancomycin after selection, while a heteroresistant phenotype (with PAP/AUC 0.9) was detected in three isolates. All isolates showed walK mutations (T188S, D235N, E261V, V380I, and G223D). Exposure to short-term shock concentrations of vancomycin promotes the formation of heteroresistance in both MRSA and MSSA. Formation of VISA phenotypes is possible during therapy with vancomycin.

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