Simulation-guided tunable DNA probe design for mismatch tolerant hybridization

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dc.citation.articleNumbere0305002en_US
dc.citation.issueNumber8en_US
dc.citation.journalTitlePLOS ONEen_US
dc.citation.volumeNumber19en_US
dc.contributor.authorBugga, Pallavien_US
dc.contributor.authorAsthana, Vishwaratnen_US
dc.contributor.authorDrezek, Rebekahen_US
dc.date.accessioned2024-10-08T13:27:48Zen_US
dc.date.available2024-10-08T13:27:48Zen_US
dc.date.issued2024en_US
dc.description.abstractThe ability to both sensitively and specifically assess the sequence composition of a nucleic acid strand is an ever-growing field. Designing a detection scheme that can perform this function when the sequence of the target being detected deviates significantly from the canonical sequence however is difficult in part because probe/primer design is based on established Watson-Crick base-pairing rules. We present here a robust and tunable toehold-based exchange probe that can detect a sequence with a variable number of SNPs of unknown identity by inserting a series of controlled, sequential mismatches into the protector seal of the toehold probe, in an effort to make the protector seal “sloppy”. We show that the mismatch-tolerant system follows predicted behavior closely even with targets containing up to four mismatches that thermodynamically deviate from the canonical sequence by up to 15 kcal/mole. The system also performs faithfully regardless of the global mismatch position on either the protector seal or target. Lastly, we demonstrate the generalizability of the approach by testing the increasingly mismatch-tolerant protectors on HIV clinical samples to show that the system is capable of resolving multiple, iteratively mutated sequences derived from numerous HIV sub-populations with remarkable precision.en_US
dc.identifier.citationBugga, P., Asthana, V., & Drezek, R. (2024). Simulation-guided tunable DNA probe design for mismatch tolerant hybridization. PLOS ONE, 19(8), e0305002. https://doi.org/10.1371/journal.pone.0305002en_US
dc.identifier.digitaljournal-pone-0305002en_US
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0305002en_US
dc.identifier.urihttps://hdl.handle.net/1911/117917en_US
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.rightsExcept where otherwise noted, this work is licensed under a Creative Commons Attribution (CC BY) license. Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleSimulation-guided tunable DNA probe design for mismatch tolerant hybridizationen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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