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Ab-initio discovery of tumoricidal oligonucleotides in a DNA sequencing machine

Noam Mamet, Itai Rusinek, Gil Harari, Zvi Shapira, Yaniv Amir, Erez Lavi, Adva Zamir, Noam Borovsky, Noah Joseph, Maria Motin, Dekel Saban, View ORCID ProfileIdo Bachelet
doi: https://doi.org/10.1101/630830
Noam Mamet
Molecular Computing Cluster, Augmanity, Rehovot, Israel. Website: https://augm.comFaculty of Life Sciences, Bar-Ilan University, Israel
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Itai Rusinek
Molecular Computing Cluster, Augmanity, Rehovot, Israel. Website: https://augm.com
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Gil Harari
Molecular Computing Cluster, Augmanity, Rehovot, Israel. Website: https://augm.com
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Zvi Shapira
Molecular Computing Cluster, Augmanity, Rehovot, Israel. Website: https://augm.com
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Yaniv Amir
Molecular Computing Cluster, Augmanity, Rehovot, Israel. Website: https://augm.com
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Erez Lavi
Molecular Computing Cluster, Augmanity, Rehovot, Israel. Website: https://augm.com
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Adva Zamir
Molecular Computing Cluster, Augmanity, Rehovot, Israel. Website: https://augm.com
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Noam Borovsky
Molecular Computing Cluster, Augmanity, Rehovot, Israel. Website: https://augm.com
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Noah Joseph
Molecular Computing Cluster, Augmanity, Rehovot, Israel. Website: https://augm.com
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Maria Motin
Molecular Computing Cluster, Augmanity, Rehovot, Israel. Website: https://augm.com
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Dekel Saban
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Ido Bachelet
Molecular Computing Cluster, Augmanity, Rehovot, Israel. Website: https://augm.com
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  • ORCID record for Ido Bachelet
  • For correspondence: ido@augm.com
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Abstract

We describe a technique for the rapid ab-initio discovery of target-tailored tumoricidal DNA oligonucleotides inside an Illumina sequencing chip. By sequencing oligonucleotide pools we generate a physical microfluidic map of hundreds of millions of potential oligo clusters, in which every cluster is mapped to a specific set of spatial coordinates. Tumor cells, pre-loaded with a fluorogenic reporter of apoptosis, are then injected into the chip and monitored over time. Apoptotic tumor cells are identified and analyzed across the entire map, automatically revealing the coordinates of oligos that induced this effect. We demonstrate this method by identifying, within just a few hours, new oligos capable of directly and selectively inducing apoptosis in primary human tumor cells. Such a major capability could lead to a new paradigm of personalized cancer therapy.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted June 16, 2019.
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Ab-initio discovery of tumoricidal oligonucleotides in a DNA sequencing machine
Noam Mamet, Itai Rusinek, Gil Harari, Zvi Shapira, Yaniv Amir, Erez Lavi, Adva Zamir, Noam Borovsky, Noah Joseph, Maria Motin, Dekel Saban, Ido Bachelet
bioRxiv 630830; doi: https://doi.org/10.1101/630830
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Ab-initio discovery of tumoricidal oligonucleotides in a DNA sequencing machine
Noam Mamet, Itai Rusinek, Gil Harari, Zvi Shapira, Yaniv Amir, Erez Lavi, Adva Zamir, Noam Borovsky, Noah Joseph, Maria Motin, Dekel Saban, Ido Bachelet
bioRxiv 630830; doi: https://doi.org/10.1101/630830

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