Cargando…

Computing in mammalian cells with nucleic acid strand exchange

DNA strand displacement has been widely used for the design of molecular circuits, motors, and sensors in cell-free settings. Recently, it has been shown that this technology can also operate in biological environments, but capabilities remain limited. Here, we look to adapt strand displacement and...

Descripción completa

Detalles Bibliográficos
Autores principales: Groves, Benjamin, Chen, Yuan-Jyue, Zurla, Chiara, Pochekailov, Sergii, Kirschman, Jonathan L., Santangelo, Philip J., Seelig, Georg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4777654/
https://www.ncbi.nlm.nih.gov/pubmed/26689378
http://dx.doi.org/10.1038/nnano.2015.278
_version_ 1782419333267324928
author Groves, Benjamin
Chen, Yuan-Jyue
Zurla, Chiara
Pochekailov, Sergii
Kirschman, Jonathan L.
Santangelo, Philip J.
Seelig, Georg
author_facet Groves, Benjamin
Chen, Yuan-Jyue
Zurla, Chiara
Pochekailov, Sergii
Kirschman, Jonathan L.
Santangelo, Philip J.
Seelig, Georg
author_sort Groves, Benjamin
collection PubMed
description DNA strand displacement has been widely used for the design of molecular circuits, motors, and sensors in cell-free settings. Recently, it has been shown that this technology can also operate in biological environments, but capabilities remain limited. Here, we look to adapt strand displacement and exchange reactions to mammalian cells and report DNA circuitry that can directly interact with a native mRNA. We began by optimizing the cellular performance of fluorescent reporters based on four-way strand exchange reactions and identified robust design principles by systematically varying the molecular structure, chemistry and delivery method. Next, we developed and tested AND and OR logic gates based on four-way strand exchange, demonstrating the feasibility of multi-input logic. Finally, we established that functional siRNA could be activated through strand exchange, and used native mRNA as programmable scaffolds for co-localizing gates and visualizing their operation with subcellular resolution.
format Online
Article
Text
id pubmed-4777654
institution National Center for Biotechnology Information
language English
publishDate 2015
record_format MEDLINE/PubMed
spelling pubmed-47776542016-06-21 Computing in mammalian cells with nucleic acid strand exchange Groves, Benjamin Chen, Yuan-Jyue Zurla, Chiara Pochekailov, Sergii Kirschman, Jonathan L. Santangelo, Philip J. Seelig, Georg Nat Nanotechnol Article DNA strand displacement has been widely used for the design of molecular circuits, motors, and sensors in cell-free settings. Recently, it has been shown that this technology can also operate in biological environments, but capabilities remain limited. Here, we look to adapt strand displacement and exchange reactions to mammalian cells and report DNA circuitry that can directly interact with a native mRNA. We began by optimizing the cellular performance of fluorescent reporters based on four-way strand exchange reactions and identified robust design principles by systematically varying the molecular structure, chemistry and delivery method. Next, we developed and tested AND and OR logic gates based on four-way strand exchange, demonstrating the feasibility of multi-input logic. Finally, we established that functional siRNA could be activated through strand exchange, and used native mRNA as programmable scaffolds for co-localizing gates and visualizing their operation with subcellular resolution. 2015-12-21 2016-03 /pmc/articles/PMC4777654/ /pubmed/26689378 http://dx.doi.org/10.1038/nnano.2015.278 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Groves, Benjamin
Chen, Yuan-Jyue
Zurla, Chiara
Pochekailov, Sergii
Kirschman, Jonathan L.
Santangelo, Philip J.
Seelig, Georg
Computing in mammalian cells with nucleic acid strand exchange
title Computing in mammalian cells with nucleic acid strand exchange
title_full Computing in mammalian cells with nucleic acid strand exchange
title_fullStr Computing in mammalian cells with nucleic acid strand exchange
title_full_unstemmed Computing in mammalian cells with nucleic acid strand exchange
title_short Computing in mammalian cells with nucleic acid strand exchange
title_sort computing in mammalian cells with nucleic acid strand exchange
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4777654/
https://www.ncbi.nlm.nih.gov/pubmed/26689378
http://dx.doi.org/10.1038/nnano.2015.278
work_keys_str_mv AT grovesbenjamin computinginmammaliancellswithnucleicacidstrandexchange
AT chenyuanjyue computinginmammaliancellswithnucleicacidstrandexchange
AT zurlachiara computinginmammaliancellswithnucleicacidstrandexchange
AT pochekailovsergii computinginmammaliancellswithnucleicacidstrandexchange
AT kirschmanjonathanl computinginmammaliancellswithnucleicacidstrandexchange
AT santangelophilipj computinginmammaliancellswithnucleicacidstrandexchange
AT seeliggeorg computinginmammaliancellswithnucleicacidstrandexchange