Utility of Multivalent Aptamers to Develop Nanoscale DNA Devices against Surface Receptors

Freage, Lina; Boykoff, Natalie; Mallikaratchy, Prabodhika

doi:10.1021/acsomega.1c01513

Cited by 10 publications

(10 citation statements)

References 44 publications

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“…DNA-based systems, specifically aptamers, serve as a promising molecular tool owing to their low cost and easily modifiable synthetic analogs with favorable pharmacokinetic properties to design modular DNA architectures. − Bispecific designs of aptamers has been evaluated for therapeutic development before. , However, to our knowledge, there are no bispecific aptamers, designs have been explored for sensing and detection. We herein demonstrated a DNA aptamer-based bispecific system to enhance the specificity of tumor cell detection by utilizing the unique biochemical composition of the TME.…”

Section: Discussionmentioning

confidence: 99%

Bispecific Aptamer Sensor toward T-Cell Leukemia Detection in the Tumor Microenvironment

et al. 2021

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The current detection methods of malignant cells are mainly based on the high expression levels of certain surface proteins on these cells. However, many of the same surface marker proteins are also expressed in normal cells. Growing evidence suggests that the molecular signatures of the tumor microenvironment (TME) are related to the biological state of a diseased cell. Exploiting the unique molecular signature of the TME, we have designed a molecular sensing agent consisting of a molecular switch that can sense the elevated concentration of a small molecule in the TME and promote precise recognition of a malignant cell. We accomplished this by designing and developing a bispecific aptamer that takes advantage of a high concentration of adenosine 5′-triphosphate in the TME. Thus, we report a prototype of a bispecific aptamer molecule, which serves as a dual detection platform and recognizes tumor cells only when a given metabolite concentration is elevated in the TME. This system overcomes hurdles in detecting tumor cells solely based on the elevated expression of cell surface markers, providing a universal platform for tumor targeting and sensing.

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Section: Discussionmentioning

confidence: 99%

Bispecific Aptamer Sensor toward T-Cell Leukemia Detection in the Tumor Microenvironment

et al. 2021

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“…DNA-based systems, specifically aptamers, serve as a promising molecular tool owing to their low cost and easily modifiable synthetic analogs with favorable pharmacokinetic properties to design modular DNA architectures. [23][24][25][26] Bispecific designs of aptamers has been evalutated for thereapeutic development before. 27,28 However, to our knowledge, there are no bispecific aptamers desgins have been explored for sensing and detection.…”

Section: Discussionmentioning

confidence: 99%

A bispecific aptamer sensor towards T-cell leukemia detection in the tumor microenvironment

Boykoff

Mallikaratchy

Lenn

et al. 2021

Preprint

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The current detection methods of malignant cells are mainly based on the high expression levels of certain surface proteins on these cells. However, many of the same surface marker proteins are also expressed in normal cells. Growing evidence suggests that the molecular signatures of the tumor microenvironment (TME) are related to the biological state of a diseased cell. Exploiting the unique molecular signature of TME, we have designed a molecular sensing agent consisting of a molecular switch that can sense the elevated concentration of a small molecule in the TME and promote precise recognition of a malignant cell. We accomplished this by designing and developing a bispecific aptamer that takes advantage of a high concentration of ATP in the TME. Thus, we report a on a prototype of a bispecific aptamer molecule, which performs as a dual detection platform and recognizes tumor cells only when a given metabolite concentration is elevated in the TME. This system overcomes hurdles in detecting tumor cells solely based on the elevated expression of cell surface markers, providing a universal platform for tumor targeting and sensing.

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“…With respect to antibodies, aptamers are cost-effective, easier to synthesize, thermally stable, and simpler to use. Of note, aptamers are now finding more and more applications in nanoscale devices for therapeutic [ 24 , 25 , 26 ] and sensing applications [ 27 , 28 , 29 , 30 , 31 ]. In particular, the combination of nanopores and aptamers has been demonstrated to be an interesting method for the development of the next generation of highly selective and multiplexed single-molecule sensing devices [ 28 , 29 , 32 , 33 , 34 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

Smart Approach for the Design of Highly Selective Aptamer-Based Biosensors

et al. 2022

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Aptamers are chemically synthesized single-stranded DNA or RNA oligonucleotides widely used nowadays in sensors and nanoscale devices as highly sensitive biorecognition elements. With proper design, aptamers are able to bind to a specific target molecule with high selectivity. To date, the systematic evolution of ligands by exponential enrichment (SELEX) process is employed to isolate aptamers. Nevertheless, this method requires complex and time-consuming procedures. In silico methods comprising machine learning models have been recently proposed to reduce the time and cost of aptamer design. In this work, we present a new in silico approach allowing the generation of highly sensitive and selective RNA aptamers towards a specific target, here represented by ammonium dissolved in water. By using machine learning and bioinformatics tools, a rational design of aptamers is demonstrated. This “smart” SELEX method is experimentally proved by choosing the best five aptamer candidates obtained from the design process and applying them as functional elements in an electrochemical sensor to detect, as the target molecule, ammonium at different concentrations. We observed that the use of five different aptamers leads to a significant difference in the sensor’s response. This can be explained by considering the aptamers’ conformational change due to their interaction with the target molecule. We studied these conformational changes using a molecular dynamics simulation and suggested a possible explanation of the experimental observations. Finally, electrochemical measurements exposing the same sensors to different molecules were used to confirm the high selectivity of the designed aptamers. The proposed in silico SELEX approach can potentially reduce the cost and the time needed to identify the aptamers and potentially be applied to any target molecule.

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Utility of Multivalent Aptamers to Develop Nanoscale DNA Devices against Surface Receptors

Cited by 10 publications

References 44 publications

Bispecific Aptamer Sensor toward T-Cell Leukemia Detection in the Tumor Microenvironment

Bispecific Aptamer Sensor toward T-Cell Leukemia Detection in the Tumor Microenvironment

A bispecific aptamer sensor towards T-cell leukemia detection in the tumor microenvironment

Smart Approach for the Design of Highly Selective Aptamer-Based Biosensors

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