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Early successes are encouraging, however, given the substantial number of distinct rare diseases, the ability to scale these successes will be unsustainable without new development efficiencies. Herein, we discuss the need for genomic newborn screening to match pace with the growing development of targeted therapeutics and ability to rapidly develop individualized therapies for rare variants. We offer approaches to move beyond conventional \u201cone disease at a time\u201d preclinical and clinical drug development and discuss planned regulatory innovations that are necessary to speed therapy delivery to individuals in need. These proposals leverage the shared properties of platform classes of therapeutics and innovative trial designs including master and platform protocols to better serve patients and accelerate drug development. Ultimately, there are risks to these novel approaches; however, we believe that close partnership and transparency between health authorities, patients, researchers, and drug developers present the path forward to overcome these challenges and deliver on the promise of gene\u2010targeted therapies for rare diseases.<\/jats:p>","DOI":"10.1002\/ajmg.c.32031","type":"journal-article","created":{"date-parts":[[2023,2,4]],"date-time":"2023-02-04T13:59:25Z","timestamp":1675519165000},"page":"30-43","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Moving away from one disease at a time: Screening, trial design, and regulatory implications of novel platform technologies"],"prefix":"10.1002","volume":"193","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4321-7376","authenticated-orcid":false,"given":"Julie","family":"Lekstrom\u2010Himes","sequence":"first","affiliation":[{"name":"Takeda  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0567-6566","authenticated-orcid":false,"given":"P J","family":"Brooks","sequence":"additional","affiliation":[{"name":"Division of Rare Diseases Research Innovation, National Center for Advancing Translational Sciences National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4513-2464","authenticated-orcid":false,"given":"Dwight D.","family":"Koeberl","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6621-1247","authenticated-orcid":false,"given":"Amy","family":"Brower","sequence":"additional","affiliation":[{"name":"American College of Medical Genetics and Genomics  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0314-0303","authenticated-orcid":false,"given":"Aaron","family":"Goldenberg","sequence":"additional","affiliation":[{"name":"Department of Bioethics Case Western Reserve University School of Medicine  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8472-0424","authenticated-orcid":false,"given":"Robert C.","family":"Green","sequence":"additional","affiliation":[{"name":"Mass General Brigham, Broad Institute Ariadne Labs and Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9026-5915","authenticated-orcid":false,"given":"Jill A.","family":"Morris","sequence":"additional","affiliation":[{"name":"National Institute of Neurological Disorders and Stroke National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph J.","family":"Orsini","sequence":"additional","affiliation":[{"name":"Wadsworth Center New York State Department of Health  Albany New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2988-7701","authenticated-orcid":false,"given":"Timothy W.","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7257-8985","authenticated-orcid":false,"given":"Erika F.","family":"Augustine","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurodevelopmental Medicine Kennedy Krieger Institute  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2,4]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31533"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1716153"},{"key":"e_1_2_13_4_1","unstructured":"Baby's First Test. 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