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Circular and linear: a tale of aptamer selection for the activation of SIRT1 to induce death in cancer cells

Al-Sudani, Basma; Ragazzon-Smith, Abby H.; Aziz, Athar; Alansari, Rania; Ferry, Natalie; Krstic-Demonacos, Marija; Ragazzon, Patricia

Circular and linear: a tale of aptamer selection for the activation of SIRT1 to induce death in cancer cells Thumbnail


Authors

Basma Al-Sudani

Abby H. Ragazzon-Smith

Athar Aziz

Rania Alansari

Natalie Ferry

Marija Krstic-Demonacos



Abstract

It is a challenge to select the right target to treat conditions without affecting non-diseased cells. Cancer belongs to the top 10 causes of death in the world and it remains difficult to treat. Amongst cancer emerging targets, silent information regulator 1 (SIRT1) – a histone deacetylase – has shown many roles in cancer, ageing and metabolism. Here we report novel SIRT1 ligands that bind and modulate the activity of SIRT1 within cells and enhance its enzymatic activity. We developed a modified aptamer capable of binding to and forming a complex with SIRT1. Our ligands are aptamers, they can be made of DNA or RNA oligonucleotides, their binding domain can recognise a target with very high affinity and specificity. We used the systematic evolution of ligands by exponential enrichment (SELEX) technique to develop circular and linear aptamers selectively binding to SIRT1. Cellular consequences of the interaction were monitored by fluorescence microscopy, cell viability assay, stability and enzymatic assays. Our results indicate that from our pool of aptamers, circular AC3 penetrates cancerous cells and is recruited to modulate the SIRT1 activity. This modulation of SIRT1 resulted in anticancer activity on different cancer cell lines. Furthermore, this modified aptamer showed no toxicity on one non-cancerous cell line and was stable in human plasma. We have demonstrated that aptamers are efficient tools for localisation of internal cell targets, and in this particular case, anticancer activity through modulation of SIRT1.

Journal Article Type Article
Acceptance Date Nov 30, 2020
Publication Date Dec 21, 2020
Publicly Available Date Mar 29, 2024
Journal RSC Advances
Print ISSN 2046-2069
Publisher Royal Society of Chemistry
Peer Reviewed Peer Reviewed
Volume 10
Issue 73
Pages 45008-45018
DOI https://doi.org/10.1039/D0RA07857C
Publisher URL https://pubs.rsc.org/en/content/articlelanding/2020/RA/D0RA07857C#!divAbstract

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