Selection of Nucleic Acid Aptamers Targeting Tumor Cell-Surface Protein Biomarkers

Mercier, Marie-Cécile; Dontenwill, Monique; Choulier, Laurence

doi:10.3390/cancers9060069

Cited by 84 publications

(50 citation statements)

References 230 publications

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“…Aptamers are typically generated from libraries of random ssDNA or RNA sequences through an in vitro iterative selection process known as SELEX (systematic evolution of ligands by exponential enrichment), which involves repetitive rounds of alternating steps of partitioning candidate oligonucleotides and their PCR amplification. 11 According to different types of targets, some variants of the SELEX procedure have been developed, such as cell/tissue SELEX, 12 , 13 , 14 , 15 protein SELEX, 16 and in vivo SELEX. 17 However, the traditional SELEX process is usually time consuming and labor intensive.…”

Section: Introductionmentioning

confidence: 99%

Molecular Recognition and In-Vitro-Targeted Inhibition of Renal Cell Carcinoma Using a DNA Aptamer

Zhang

Wang

Xie

et al. 2018

Molecular Therapy - Nucleic Acids

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Renal cell carcinoma (RCC) is the most common malignant tumor of the urinary system, and it has a high frequency of local invasion and distant metastasis. Although multiple advances have been made in the diagnosis and therapy of RCC, the vast majority of patients with metastatic RCC remain incurable. In this study, an aptamer named SW-4 against RCC 786-O cells was identified from a known sequence pool. The identified aptamer exhibited high binding affinity for target cells with dissociation constants in the nanomolar range. Binding analysis revealed that SW-4 only bound to RCC 786-O cells, but not HEK293T cells or human proximal tubular HK-2 cells, indicating that SW-4 has excellent binding selectivity. By sequence optimization, the 26-nt truncated SW-4b demonstrated improved binding affinity, and it was internalized into target cells via caveolae-mediated endocytosis in a temperature-dependent manner. Furthermore, fluorescence imaging confirmed that SW-4b accumulated at tumor sites in 786-O xenograft nude mice models and specifically recognized clinical RCC tissues. Meanwhile, SW-4b inhibited proliferation of 786-O cells by arresting cell cycle progression at the S phase. Taken together, these results indicate that SW-4b is a potential candidate for development into a novel tool for diagnosis and targeted therapy of RCC.

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Section: Introductionmentioning

confidence: 99%

Molecular Recognition and In-Vitro-Targeted Inhibition of Renal Cell Carcinoma Using a DNA Aptamer

Zhang

Wang

Xie

et al. 2018

Molecular Therapy - Nucleic Acids

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“…A wide variety of oligonucleotide substitutions are now available, and these methods have been exhaustively reviewed in several recent articles [ 7 , 8 , 184 , 187 ] and older publications [ 188 , 189 , 190 ]. The review by Zhou and Rossi published a few months ago is particularly thorough.…”

Section: Discussionmentioning

confidence: 99%

Development of Phosphorothioate DNA and DNA Thioaptamers

Volk

Lokesh

2017

Biomedicines

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Nucleic acid aptamers are short RNA- or DNA-based affinity reagents typically selected from combinatorial libraries to bind to a specific target such as a protein, a small molecule, whole cells or even animals. Aptamers have utility in the development of diagnostic, imaging and therapeutic applications due to their size, physico-chemical nature and ease of synthesis and modification to suit the application. A variety of oligonucleotide modifications have been used to enhance the stability of aptamers from nuclease degradation in vivo. The non-bridging oxygen atoms of the phosphodiester backbones of RNA and DNA aptamers can be substituted with one or two sulfur atoms, resulting in thioaptamers with phosphorothioate or phosphorodithioate linkages, respectively. Such thioaptamers are known to have increased binding affinity towards their target, as well as enhanced resistance to nuclease degradation. In this review, we discuss the development of phosphorothioate chemistry and thioaptamers, with a brief review of selection methods.

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“…Aptamers generated against cell markers with traditional SELEX vastly outnumbers aptamers generated by Cell-SELEX. Only a few cell-specific aptamers are presented in this section as more detailed reviews are available [ 71 , 72 ]. Determining the binding affinity aptamers that were developed against a surface cell marker can be achieved with fluorescence/confocal microscopy and flow cytometry, such as the aptamers developed against the Epithelial cell adhesion molecule [ 73 ] and CD44 [ 74 ].…”

Section: Aptamers Developed Against Cell-specific Markersmentioning

confidence: 99%

Development of Cell-Specific Aptamers: Recent Advances and Insight into the Selection Procedures

et al. 2017

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Systematic evolution of ligands by exponential enrichment (SELEX) is an established procedure for developing short single-stranded nucleic acid ligands called aptamers against a target of choice. This approach has also been used for developing aptamers specific to whole cells named Cell-SELEX. Aptamers selected by Cell-SELEX have the potential to act as cell specific therapeutics, cell specific markers or cell specific drug delivery and imaging agents. However, aptamer development is a laborious and time-consuming process which is often challenging due to the requirement of frequent optimization of various steps involved in Cell-SELEX procedures. This review provides an insight into various procedures for selection, aptamer enrichment, regeneration and aptamer-binding analysis, in addition to a very recent update on all aptamers selected by Cell-SELEX procedures.

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Selection of Nucleic Acid Aptamers Targeting Tumor Cell-Surface Protein Biomarkers

Cited by 84 publications

References 230 publications

Molecular Recognition and In-Vitro-Targeted Inhibition of Renal Cell Carcinoma Using a DNA Aptamer

Molecular Recognition and In-Vitro-Targeted Inhibition of Renal Cell Carcinoma Using a DNA Aptamer

Development of Phosphorothioate DNA and DNA Thioaptamers

Development of Cell-Specific Aptamers: Recent Advances and Insight into the Selection Procedures

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