Development and characterization of a DNA aptamer for MLL-AF9 expressing acute myeloid leukemia cells using whole cell-SELEX

Earnest, Kaylin G.; McConnell, Erin M.; Hassan, Eman; Wunderlich, Mark; Hosseinpour, Bahareh; Bono, Bianca S. M.; Chee, Melissa J.; Mulloy, James C.; Willmore, William G.; DeRosa, Maria C.; Merino, Edward J.

doi:10.1038/s41598-021-98676-4

Cited by 10 publications

(4 citation statements)

References 69 publications

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“…We identified structural regions that account for the binding motifs of the full-length aptamers. The constant regions of aptamer sequences have often been found to participate in the functional secondary structures by interacting with the random region [ 28 , 29 , 30 , 31 ]. We also found that in the three short aptamers, the 5′ priming sequence is partly involved in the functional binding site.…”

Section: Discussionmentioning

confidence: 99%

Optimization of Short RNA Aptamers for TNBC Cell Targeting

Camorani

d’Argenio

Agnello

et al. 2022

IJMS

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Triple-negative breast cancer (TNBC) is an aggressive cancer with limited targeted therapies. RNA aptamers, suitably chemically modified, work for therapeutic purposes in the same way as antibodies. We recently generated 2′Fluoro-pyrimidines RNA-aptamers that act as effective recognition elements for functional surface signatures of TNBC cells. Here, we optimized three of them by shortening and proved the truncated aptamers as optimal candidates to enable active targeting to TNBC. By using prediction of secondary structure to guide truncation, we identified structural regions that account for the binding motifs of the full-length aptamers. Their chemical synthesis led to short aptamers with superb nuclease resistance, which specifically bind to TNBC target cells and rapidly internalize into acidic compartments. They interfere with the growth of TNBC cells as mammospheres, thus confirming their potential as anti-tumor agents. We propose sTN145, sTN58 and sTN29 aptamers as valuable tools for selective TNBC targeting and promising candidates for effective treatments, including therapeutic agents and targeted delivery nanovectors.

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Section: Discussionmentioning

confidence: 99%

Optimization of Short RNA Aptamers for TNBC Cell Targeting

Camorani

d’Argenio

Agnello

et al. 2022

IJMS

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“…The stem-loop structure can stabilize and support the conformation of aptamers. Therefore, in case the existence of the stem-loop structure, the primer binding region should not be removed directly to avoid destroying the conformation of aptamers [ 63 , 64 ]. However, when the selected aptamers contain many stems or loops, the complex conformation may also affect the binding of aptamers and targets.…”

Section: Post-selex Optimization Of Aptamersmentioning

confidence: 99%

Systematic bio-fabrication of aptamers and their applications in engineering biology

Cai

Chen

Zhang

et al. 2022

Syst Microbiol and Biomanuf

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Aptamers are single-stranded DNA or RNA molecules that have high affinity and selectivity to bind to specific targets. Compared to antibodies, aptamers are easy to in vitro synthesize with low cost, and exhibit excellent thermal stability and programmability. With these features, aptamers have been widely used in biology and medicine-related fields. In the meantime, a variety of systematic evolution of ligands by exponential enrichment (SELEX) technologies have been developed to screen aptamers for various targets. According to the characteristics of targets, customizing appropriate SELEX technology and post-SELEX optimization helps to obtain ideal aptamers with high affinity and specificity. In this review, we first summarize the latest research on the systematic bio-fabrication of aptamers, including various SELEX technologies, post-SELEX optimization, and aptamer modification technology. These procedures not only help to gain the aptamer sequences but also provide insights into the relationship between structure and function of the aptamers. The latter provides a new perspective for the systems bio-fabrication of aptamers. Furthermore, on this basis, we review the applications of aptamers, particularly in the fields of engineering biology, including industrial biotechnology, medical and health engineering, and environmental and food safety monitoring. And the encountered challenges and prospects are discussed, providing an outlook for the future development of aptamers.

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“…They can interact with their targets through their unique three-dimensional (3D) conformations, and specific aptamers against various targets like peptides, proteins, small inorganic ions, various complex tissues or cells, and drugs have been successfully developed . Aptamers developed from random nucleotide libraries by SELEX possess high selectivity to their molecular or cellular targets and typically bind to their targets with mid-to-low nanomolar affinity. , Therefore, aptamers are a promising analytical tool and alternative to antibodies for the detection of small molecules, proteins, viruses, whole cells, and peptides. − Aptamers have greater thermal stability than antibodies, and they can be stored at ambient temperatures . In addition, aptamer affinities are not affected by labeling because labels can be incorporated at the time of aptamer synthesis in defined positions away from binding loops .…”

Section: Introductionmentioning

confidence: 99%

Isolation and Identification of the High-Affinity DNA Aptamer Target to the Brain-Derived Neurotrophic Factor (BDNF)

Chowdhury,

Collins,

Gell

et al. 2023

ACS Chem. Neurosci.

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Aptamers are functional oligonucleotide ligands used for the molecular recognition of various targets. The natural characteristics of aptamers make them an excellent alternative to antibodies in diagnostics, therapeutics, and biosensing. DNA aptamers are mainly single-stranded oligonucleotides (ssDNA) that possess a definite binding to targets. However, the application of aptamers to the fields of brain health and neurodegenerative diseases has been limited to date. Herein, a DNA aptamer against the brain-derived neurotrophic factor (BDNF) protein was obtained by in vitro selection. BDNF is a potential biomarker of brain health and neurodegenerative diseases and has functions in the synaptic plasticity and survival of neurons. We identified eight aptamers that have binding affinity for BDNF from a 50-nucleotide library. Among these aptamers, NV_B12 showed the highest sensitivity and selectivity for detecting BDNF. In an aptamer-linked immobilized sorbent assay (ALISA), the NV_B12 aptamer strongly bound to BDNF protein, in a dose-dependent manner. The dissociation constant (K d ) for NV_B12 was 0.5 nM (95% CI: 0.4−0.6 nM). These findings suggest that BDNF-specific aptamers could be used as an alternative to antibodies in diagnostic and detection assays for BDNF.

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Development and characterization of a DNA aptamer for MLL-AF9 expressing acute myeloid leukemia cells using whole cell-SELEX

Cited by 10 publications

References 69 publications

Optimization of Short RNA Aptamers for TNBC Cell Targeting

Optimization of Short RNA Aptamers for TNBC Cell Targeting

Systematic bio-fabrication of aptamers and their applications in engineering biology

Isolation and Identification of the High-Affinity DNA Aptamer Target to the Brain-Derived Neurotrophic Factor (BDNF)

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