Aptamers in hematological malignancies and their potential therapeutic implications

Ouyang, Wanyan; Yu, Ziqiang; Zhao, Xiaohong; Lu, Shiyun; Wang, Zhi

doi:10.1016/j.critrevonc.2016.08.003

Cited by 7 publications

(9 citation statements)

References 121 publications

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“…Such chemical modifications of the DNA backbone provide resistance against nucleases, as was first shown by Eckstein’s group [ 17 ], and often increase binding affinity [ 16 ]. The introduction of functional groups in the aptamer backbone permits conjugation to other drugs, siRNA [ 18 , 19 ], and nanoparticles [ 20 , 21 , 22 ], further broadening their application as multivalent therapeutics [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ].…”

Section: Advantages Of Aptamersmentioning

confidence: 99%

Aptamer Therapeutics in Cancer: Current and Future

Morita

Leslie

Kameyama

et al. 2018

Cancers

171

112

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Aptamer-related technologies represent a revolutionary advancement in the capacity to rapidly develop new classes of targeting ligands. Structurally distinct RNA and DNA oligonucleotides, aptamers mimic small, protein-binding molecules and exhibit high binding affinity and selectivity. Although their molecular weight is relatively small—approximately one-tenth that of monoclonal antibodies—their complex tertiary folded structures create sufficient recognition surface area for tight interaction with target molecules. Additionally, unlike antibodies, aptamers can be readily chemically synthesized and modified. In addition, aptamers’ long storage period and low immunogenicity are favorable properties for clinical utility. Due to their flexibility of chemical modification, aptamers are conjugated to other chemical entities including chemotherapeutic agents, siRNA, nanoparticles, and solid phase surfaces for therapeutic and diagnostic applications. However, as relatively small sized oligonucleotides, aptamers present several challenges for successful clinical translation. Their short plasma half-lives due to nuclease degradation and rapid renal excretion necessitate further structural modification of aptamers for clinical application. Since the US Food and Drug Administration (FDA) approval of the first aptamer drug, Macugen® (pegaptanib), which treats wet-age-related macular degeneration, several aptamer therapeutics for oncology have followed and shown promise in pre-clinical models as well as clinical trials. This review discusses the advantages and challenges of aptamers and introduces therapeutic aptamers under investigation and in clinical trials for cancer treatments.

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Section: Advantages Of Aptamersmentioning

confidence: 99%

Aptamer Therapeutics in Cancer: Current and Future

Morita

Leslie

Kameyama

et al. 2018

Cancers

171

112

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“…Unbound sequences are washed away, while bound sequences are first eluted by heating and subsequently incubated with cells not expressing targeted proteins for counterselection. Afterwards, unbound sequences, which do not recognize non-specific targets on negative cells, are later reverse transcript and amplified by PCR [3]. However, cell-SELEX requires suitable cell lines expressing or not the targeted proteins for positive and negative selection, respectively, and aptamer specificity remains lower than that obtained by SELEX process [4].…”

Section: Aptamers and Modified Aptamersmentioning

confidence: 99%

“…Spiegelmers, modified RNA aptamers in an L-configuration (Spiegel = mirror), have higher stability and affinity as compared with standard RNA aptamers; in particular, spiegelmers are more resistant to nuclease degradation and can hybridize with nucleic acids at very low rates [3]. Therefore, spiegelmers can have a longer half-life in body fluids with better pharmacokinetics and pharmacodynamics (PK/PD) properties as compared with standard aptamers, thus, making these molecules more suitable for drug delivery or as anticancer agents.…”

Section: Aptamers and Modified Aptamersmentioning

confidence: 99%

“…In addition, BCR-ABL can also increase the expression of several pro-inflammatory cytokines and growth factors [67]. β-arrestins which are scaffolding proteins for regulation of signal transduction at G protein-coupled receptors are essential for the activation of the Hedgehog/Smoothened and Wingless/Frizzled signaling pathways which are crucial for normal hematopoiesis and seem to be involved in CML pathogenesis [3].…”

Section: Chronic Myeloid Leukemiamentioning

confidence: 99%

“…The emerging of highly specific molecular and immunological diagnostic technologies helps hematologists to increase their knowledge of disease pathophysiology and to improve clinical management of patients [1]. Aptamers short three-dimensional RNA or single-stranded DNA oligonucleotides or antisense oligonucleotides (ASOs) can interact to a variety of targets with high affinity and specificity, and thus can be used for analytical or diagnostic applications in the hematologic field [3][4][5][6][7]. In this review, we summarize current applications of aptamers and antisense oligonucleotides in malignant and non-malignant hematological diseases.…”

Section: Introductionmentioning

confidence: 99%

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Aptamers and Antisense Oligonucleotides for Diagnosis and Treatment of Hematological Diseases

Giudice

Mensitieri

Izzo

et al. 2020

IJMS

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Aptamers or chemical antibodies are single-stranded DNA or RNA oligonucleotides that bind proteins and small molecules with high affinity and specificity by recognizing tertiary or quaternary structures as antibodies. Aptamers can be easily produced in vitro through a process known as systemic evolution of ligands by exponential enrichment (SELEX) or a cell-based SELEX procedure. Aptamers and modified aptamers, such as slow, off-rate, modified aptamers (SOMAmers), can bind to target molecules with less polar and more hydrophobic interactions showing slower dissociation rates, higher stability, and resistance to nuclease degradation. Aptamers and SOMAmers are largely employed for multiplex high-throughput proteomics analysis with high reproducibility and reliability, for tumor cell detection by flow cytometry or microscopy for research and clinical purposes. In addition, aptamers are increasingly used for novel drug delivery systems specifically targeting tumor cells, and as new anticancer molecules. In this review, we summarize current preclinical and clinical applications of aptamers in malignant and non-malignant hematological diseases.

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Aptamer-Based Affinity Chromatography for Protein Extraction and Purification

Perret

Boschetti²

2019

Advances in Biochemical Engineering/Biotechnology

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Aptamers in hematological malignancies and their potential therapeutic implications

Cited by 7 publications

References 121 publications

Aptamer Therapeutics in Cancer: Current and Future

Aptamer Therapeutics in Cancer: Current and Future

Aptamers and Antisense Oligonucleotides for Diagnosis and Treatment of Hematological Diseases

Aptamer-Based Affinity Chromatography for Protein Extraction and Purification

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