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

Abstract Current classes of cancer therapeutics have negative side effects stemming from off-target cytotoxicity. One way to avoid this would be to use a drug delivery system decorated with targeting moieties, such as an aptamer, if a targeted aptamer is available. In this study, aptamers were selec...

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Autores principales:	Kaylin G. Earnest, Erin M. McConnell, Eman M. Hassan, Mark Wunderlich, Bahareh Hosseinpour, Bianca S. Bono, Melissa J. Chee, James C. Mulloy, William G. Willmore, Maria C. DeRosa, Edward J. Merino
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/17d8b5d0007c474daed087ef61f4e1db
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spelling	oai:doaj.org-article:17d8b5d0007c474daed087ef61f4e1db2021-12-02T17:17:39ZDevelopment and characterization of a DNA aptamer for MLL-AF9 expressing acute myeloid leukemia cells using whole cell-SELEX10.1038/s41598-021-98676-42045-2322https://doaj.org/article/17d8b5d0007c474daed087ef61f4e1db2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98676-4https://doaj.org/toc/2045-2322Abstract Current classes of cancer therapeutics have negative side effects stemming from off-target cytotoxicity. One way to avoid this would be to use a drug delivery system decorated with targeting moieties, such as an aptamer, if a targeted aptamer is available. In this study, aptamers were selected against acute myeloid leukemia (AML) cells expressing the MLL-AF9 oncogene through systematic evolution of ligands by exponential enrichment (SELEX). Twelve rounds of SELEX, including two counter selections against fibroblast cells, were completed. Aptamer pools were sequenced, and three candidate sequences were identified. These sequences consisted of two 23-base primer regions flanking a 30-base central domain. Binding studies were performed using flow cytometry, and the lead sequence had a binding constant of 37.5 + / − 2.5 nM to AML cells, while displaying no binding to fibroblast or umbilical cord blood cells at 200 nM. A truncation study of the lead sequence was done using nine shortened sequences, and showed the 5′ primer was not important for binding. The lead sequence was tested against seven AML patient cultures, and five cultures showed binding at 200 nM. In summary, a DNA aptamer specific to AML cells was developed and characterized for future drug-aptamer conjugates.Kaylin G. EarnestErin M. McConnellEman M. HassanMark WunderlichBahareh HosseinpourBianca S. BonoMelissa J. CheeJames C. MulloyWilliam G. WillmoreMaria C. DeRosaEdward J. MerinoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kaylin G. Earnest Erin M. McConnell Eman M. Hassan Mark Wunderlich Bahareh Hosseinpour Bianca S. Bono Melissa J. Chee James C. Mulloy William G. Willmore Maria C. DeRosa Edward J. Merino Development and characterization of a DNA aptamer for MLL-AF9 expressing acute myeloid leukemia cells using whole cell-SELEX
description	Abstract Current classes of cancer therapeutics have negative side effects stemming from off-target cytotoxicity. One way to avoid this would be to use a drug delivery system decorated with targeting moieties, such as an aptamer, if a targeted aptamer is available. In this study, aptamers were selected against acute myeloid leukemia (AML) cells expressing the MLL-AF9 oncogene through systematic evolution of ligands by exponential enrichment (SELEX). Twelve rounds of SELEX, including two counter selections against fibroblast cells, were completed. Aptamer pools were sequenced, and three candidate sequences were identified. These sequences consisted of two 23-base primer regions flanking a 30-base central domain. Binding studies were performed using flow cytometry, and the lead sequence had a binding constant of 37.5 + / − 2.5 nM to AML cells, while displaying no binding to fibroblast or umbilical cord blood cells at 200 nM. A truncation study of the lead sequence was done using nine shortened sequences, and showed the 5′ primer was not important for binding. The lead sequence was tested against seven AML patient cultures, and five cultures showed binding at 200 nM. In summary, a DNA aptamer specific to AML cells was developed and characterized for future drug-aptamer conjugates.
format	article
author	Kaylin G. Earnest Erin M. McConnell Eman M. Hassan Mark Wunderlich Bahareh Hosseinpour Bianca S. Bono Melissa J. Chee James C. Mulloy William G. Willmore Maria C. DeRosa Edward J. Merino
author_facet	Kaylin G. Earnest Erin M. McConnell Eman M. Hassan Mark Wunderlich Bahareh Hosseinpour Bianca S. Bono Melissa J. Chee James C. Mulloy William G. Willmore Maria C. DeRosa Edward J. Merino
author_sort	Kaylin G. Earnest
title	Development and characterization of a DNA aptamer for MLL-AF9 expressing acute myeloid leukemia cells using whole cell-SELEX
title_short	Development and characterization of a DNA aptamer for MLL-AF9 expressing acute myeloid leukemia cells using whole cell-SELEX
title_full	Development and characterization of a DNA aptamer for MLL-AF9 expressing acute myeloid leukemia cells using whole cell-SELEX
title_fullStr	Development and characterization of a DNA aptamer for MLL-AF9 expressing acute myeloid leukemia cells using whole cell-SELEX
title_full_unstemmed	Development and characterization of a DNA aptamer for MLL-AF9 expressing acute myeloid leukemia cells using whole cell-SELEX
title_sort	development and characterization of a dna aptamer for mll-af9 expressing acute myeloid leukemia cells using whole cell-selex
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/17d8b5d0007c474daed087ef61f4e1db
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Development and characterization of a DNA aptamer for MLL-AF9 expressing acute myeloid leukemia cells using whole cell-SELEX

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