{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T03:01:08Z","timestamp":1791082868808,"version":"4.1.0"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"18","license":[{"start":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T00:00:00Z","timestamp":1725840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN184073-18"],"award-info":[{"award-number":["RGPIN184073-18"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2020-06401"],"award-info":[{"award-number":["RGPIN-2020-06401"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["VR2-172718"],"award-info":[{"award-number":["VR2-172718"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The 10\u201323 DNAzyme is one of the most active DNA-based enzymes, and in theory, can be designed to target any purine-pyrimidine junction within an RNA sequence for cleavage. However, purine-pyrimidine junctions within a large, structured RNA (lsRNA) molecule of biological origin are not always accessible to 10\u201323, negating its general utility as an RNA-cutting molecular scissor. Herein, we report a generalizable strategy that allows 10\u201323 to access any purine-pyrimidine junction within an lsRNA. Using three large SARS-CoV-2 mRNA sequences of 566, 584 and 831 nucleotides in length as model systems, we show that the use of antisense DNA oligonucleotides (ASOs) that target the upstream and downstream regions flanking the cleavage site can restore the activity (kobs) of previously poorly active 10\u201323 DNAzyme systems by up to 2000-fold. We corroborated these findings mechanistically using in-line probing to demonstrate that ASOs reduced 10\u201323 DNAzyme target site structure within the lsRNA substrates. This approach represents a simple, efficient, cost-effective, and generalizable way to improve the accessibility of 10\u201323 to a chosen target site within an lsRNA molecule, especially where direct access to the genomic RNA target is necessary.<\/jats:p>","DOI":"10.1093\/nar\/gkae778","type":"journal-article","created":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T10:43:23Z","timestamp":1725878603000},"page":"11177-11187","source":"Crossref","is-referenced-by-count":26,"title":["Making target sites in large structured RNAs accessible to RNA-cleaving DNAzymes through hybridization with synthetic DNA oligonucleotides"],"prefix":"10.1093","volume":"52","author":[{"given":"Connor","family":"Nurmi","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University , Ontario L8S 4L8 ,","place":["Canada"]},{"name":"Biointerfaces Institute, McMaster University , Ontario L8S 4L8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimmy","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University , Ontario L8S 4L8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"Mathai","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University , Ontario L8S 4L8 ,","place":["Canada"]},{"name":"Biointerfaces Institute, McMaster University , Ontario L8S 4L8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3461-9824","authenticated-orcid":false,"given":"John\u00a0D","family":"Brennan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University , Ontario L8S 4L8 ,","place":["Canada"]},{"name":"Biointerfaces Institute, McMaster University , Ontario L8S 4L8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7533-6743","authenticated-orcid":false,"given":"Yingfu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University , Ontario L8S 4L8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,9,9]]},"reference":[{"key":"2024101409524222600_B1","doi-asserted-by":"crossref","first-page":"8954","DOI":"10.1039\/D1CS00240F","article-title":"Biosensing with DNAzymes","volume":"50","author":"McConnell","year":"2021","journal-title":"Chem. 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