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Here, a novel approach for amplifying DNA with multiarm priming and looping optimization of nucleic acid (AMPLON) is presented. AMPLON relies on a novel polymeric material with unique set of multiarm polyethylene glycol\u2013DNA primers for efficient DNA amplification under isothermal conditions. Each arm carries single\u2010stranded DNA complementing the sense or antisense sequence of the target DNA. The amplification reaction begins with antisense arms binding to the target DNA, forming a template for sense\u2010carrying arms to direct multiarm large DNA amplicon synthesis through successive DNA looping and unlooping steps. Using human immunodeficiency virus type 1 (HIV\u20101) as a model clinical target, AMPLON exhibits high sensitivity, detecting target concentrations as low as 100 copies mL<jats:sup>\u22121<\/jats:sup>. Compared to a quantitative real\u2010time polymerase chain reaction assay using sensitive primers, AMPLON reliably identifies HIV\u20101 RNA in plasma samples (<jats:italic>n<\/jats:italic> = 20) with a significant agreement rate of 95%. With its ability to achieve highly specific and sensitive target amplification within 30 min, AMPLON holds immense potential to transform the field of nucleic acid research and unleashing new possibilities in medicine and biotechnology.<\/jats:p>","DOI":"10.1002\/adma.202311634","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T20:09:44Z","timestamp":1713989384000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["AMPLON: Amplifying DNA with Multiarm Priming and Looping Optimization of Nucleic Acid"],"prefix":"10.1002","volume":"36","author":[{"given":"Mert Tunca","family":"Doganay","sequence":"first","affiliation":[{"name":"Department of Medicine Case Western Reserve University School of Medicine  Cleveland OH 44106 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan","family":"Roman","sequence":"additional","affiliation":[{"name":"Department of Medicine Case Western Reserve University School of Medicine  Cleveland OH 44106 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea M.","family":"Hujer","sequence":"additional","affiliation":[{"name":"Department of Medicine Case Western Reserve University School of Medicine  Cleveland OH 44106 USA"},{"name":"Research Service Louis Stokes Cleveland Department of Veterans Affairs Medical Center Cleveland OH 44106 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Bonomo","sequence":"additional","affiliation":[{"name":"Department of Medicine Case Western Reserve University School of Medicine  Cleveland OH 44106 USA"},{"name":"Research Service Louis Stokes Cleveland Department of Veterans Affairs Medical Center Cleveland OH 44106 USA"},{"name":"Molecular Biology and Microbiology Case Western Reserve University School of Medicine Cleveland OH 44106 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven G.","family":"Deeks","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California San Francisco CA 94110 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel R.","family":"Kuritzkes","sequence":"additional","affiliation":[{"name":"Department of Medicine Harvard Medical School  Boston MA 02115 USA"},{"name":"Division of Infectious Diseases Brigham and Women's Hospital Harvard Medical School  Boston MA 02139 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5433-384X","authenticated-orcid":false,"given":"Mohamed S.","family":"Draz","sequence":"additional","affiliation":[{"name":"Department of Medicine Case Western Reserve University School of Medicine  Cleveland OH 44106 USA"},{"name":"Molecular Biology and Microbiology Case Western Reserve University School of Medicine Cleveland OH 44106 USA"},{"name":"Department of Biomedical Engineering Case Western Reserve University Cleveland OH 44106 USA"},{"name":"Department of Biomedical Engineering Cleveland Clinic  Cleveland OH 44106 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,6]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1296-1668"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/422028a"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03195"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1249"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2017.04.005"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08605"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6941.2008.00629.x"},{"key":"e_1_2_9_8_1","first-page":"76","volume":"11","author":"Mead D. 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