Selection of DNA aptamers that bind to influenza A viruses with high affinity and broad subtype specificity

Shiratori, Ikuo; Akitomi, Joe; Boltz, David A.; Horii, Katsunori; Furuichi, Makio; Waga, Iwao

doi:10.1016/j.bbrc.2013.11.041

Cited by 88 publications

(70 citation statements)

References 19 publications

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“…Sequences from the third and fourth round of selection actually showed less variability (Table S1). Some other studies also noticed and discussed this kind of phenomenon when selecting for RNA and DNA aptamers (45)(46)(47).…”

Section: Discussionmentioning

confidence: 99%

The isolation of an RNA aptamer targeting to p53 protein with single amino acid mutation

Liang

Farooq

Shah

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

102

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p53, known as a tumor suppressor, is a DNA binding protein that regulates cell cycle, activates DNA repair proteins, and triggers apoptosis in multicellular animals. More than 50% of human cancers contain a mutation or deletion of the p53 gene, and p53R175 is one of the hot spots of p53 mutation. Nucleic acid aptamers are short singlestranded oligonucleotides that are able to bind various targets, and they are typically isolated from an experimental procedure called systematic evolution of ligand exponential enrichment (SELEX). Using a previously unidentified strategy of contrast screening with SELEX, we have isolated an RNA aptamer targeting p53R175H. This RNA aptamer (p53R175H-APT) has a significantly stronger affinity to p53R175H than to the wild-type p53 in both in vitro and in vivo assays. p53R175H-APT decreased the growth rate, weakened the migration capability, and triggered apoptosis in human lung cancer cells harboring p53R175H. Further analysis actually indicated that p53R175H-APT might partially rescue or correct the p53R175H to function more like the wild-type p53. In situ injections of p53R175H-APT to the tumor xenografts confirmed the effects of this RNA aptamer on p53R175H mutation in mice.p53 | RNA aptamer | contrast screening | SELEX | tumor N ucleic acid aptamers, as single-stranded DNA or RNA oligonucleotides that are able to bind various targets with high specificity, were first isolated from a pool of random sequences with a process called systematic evolution of ligand exponential enrichment (SELEX) in 1990 by two laboratories (1, 2). Over the years, an array of methods have been invented to facilitate SELEX screening, and specific aptamers binding to partners ranging from small molecules to large proteins have been isolated. However, an RNA aptamer that can distinguish a protein with a single amino acid mutation from the wild-type (WT) protein remains absent (3-11).Protein with a single amino acid substitution is the cause of a plethora of human diseases (12)(13)(14). A well-known example is sickle-cell anemia, which is caused by a point mutation in the β-globin chain of hemoglobin (15). Also, point mutations in multiple tumor suppressor proteins cause cancer (16-18). The protein p53 is a tumor suppressor and functions as a transcription factor to regulate the expression of genes involved in DNA repair, cell cycle, and apoptosis. A mutation within one allele of this gene can result in inactivation of the remaining WT allele in a dominant-negative manner, and mutations from six mutation hot spots located in the DNA-binding surface of p53 are frequently found in almost all cancer types (19). Actually, more than half of human cancer cases relate to mutations in p53, and the single amino acid substitution p53R175H is one of the mutations at the p53R175 hot spot (20,21). R175H mutation abolishes the p53 WT functions in both MEF cells and thymocytes (22). p53R175H possesses a marked anti-apoptotic gain-of-function in lung cancer cells (23). Also, p53R175H cooperates better than any other mutant ...

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Section: Discussionmentioning

confidence: 99%

The isolation of an RNA aptamer targeting to p53 protein with single amino acid mutation

Liang

Farooq

Shah

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

102

View full text Add to dashboard Cite

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“…Aptamers have already been produced for a wide variety of viruses. A few prominent examples are HIV [129,130], HepBV [131], EBOV [132], severe acute respiratory syndrome (SARS) [133,134], norovirus [135], rabies virus [136], vaccinia virus [137,138], dengue virus [128], and influenza viruses [139,140].…”

Section: Aptamersmentioning

confidence: 99%

Gravimetric Viral Diagnostics: QCM Based Biosensors for Early Detection of Viruses

et al. 2017

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Viruses are pathogenic microorganisms that can inhabit and replicate in human bodies causing a number of widespread infectious diseases such as influenza, gastroenteritis, hepatitis, meningitis, pneumonia, acquired immune deficiency syndrome (AIDS) etc. A majority of these viral diseases are contagious and can spread from infected to healthy human beings. The most important step in the treatment of these contagious diseases and to prevent their unwanted spread is to timely detect the disease-causing viruses. Gravimetric viral diagnostics based on quartz crystal microbalance (QCM) transducers and natural or synthetic receptors are miniaturized sensing platforms that can selectively recognize and quantify harmful virus species. Herein, a review of the label-free QCM virus sensors for clinical diagnostics and point of care (POC) applications is presented with major emphasis on the nature and performance of different receptors ranging from the natural or synthetic antibodies to selective macromolecular materials such as DNA and aptamers. A performance comparison of different receptors is provided and their limitations are discussed.

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“…The selected DNA aptamers: RHA0006, RH0385 and RHA1635 were able to successfully bind the three mentioned IVA subtypes. RHA0006 and RH0385 were also used in a sandwich enzyme-linked aptamer assay (ELAA), developing a novel, rapid and cost-effective diagnostic tool to identify various IVA subtypes [68].…”

Section: Influenza a Virus (Iav)mentioning

confidence: 99%

Application of Nucleic Acid Aptamers to Viral Detection and Inhibition

Leija-Montoya¹,

Benítez‐Hess²,

Álvarez-Salas³

2016

Nucleic Acids - From Basic Aspects to Laboratory Tools

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Nucleic acid aptamers are small oligonucleotides that specifically bind to other molecules through noncovalent interactions that rely on complex tridimensional structural arrangements. Aptamers are generated through the iterative in vitro selection method called SE-LEX, resulting in specific binding against a wide variety of molecular targets including viruses. Because aptamers are obtained in vitro and can be synthetically produced, they have been envisioned as future diagnostic and therapeutic tools for human diseases including virus-borne pathologies. Aptamers have been isolated against a number of viruses including pandemic influenza virus, human papillomavirus and hepatitis C virus. Although aptamers have proven themselves as extremely sensitive detection tools triggering the development of affordable and highly diagnostic methods, their use as therapeutic moieties has been hampered by biostability, delivery and pharmacodynamical issues. Nevertheless, a new generation of chemically modified aptamers shows promise for the coming of age of protein-targeted noncatalytic oligonucleotides for the therapy of viral disease. The present review focuses on the most successful antiviral aptamers reported and includes a description of some of the novel methods developed for their use as diagnostic and therapeutic tools

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Selection of DNA aptamers that bind to influenza A viruses with high affinity and broad subtype specificity

Cited by 88 publications

References 19 publications

The isolation of an RNA aptamer targeting to p53 protein with single amino acid mutation

The isolation of an RNA aptamer targeting to p53 protein with single amino acid mutation

Gravimetric Viral Diagnostics: QCM Based Biosensors for Early Detection of Viruses

Application of Nucleic Acid Aptamers to Viral Detection and Inhibition

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