{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T21:50:08Z","timestamp":1772229008468,"version":"3.50.1"},"reference-count":154,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CICS-UBI","award":["UIDB\/00709\/2020"],"award-info":[{"award-number":["UIDB\/00709\/2020"]}]},{"name":"CICS-UBI","award":["UIDP\/00709\/2020"],"award-info":[{"award-number":["UIDP\/00709\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT)\/MCTES (PIDDAC)","award":["UIDB\/00709\/2020"],"award-info":[{"award-number":["UIDB\/00709\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT)\/MCTES (PIDDAC)","award":["UIDP\/00709\/2020"],"award-info":[{"award-number":["UIDP\/00709\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Monogenic disorders are a group of human diseases caused by mutations in single genes. While some disease-altering treatments offer relief and slow the progression of certain conditions, the majority of monogenic disorders still lack effective therapies. In recent years, gene therapy has appeared as a promising approach for addressing genetic disorders. However, despite advancements in gene manipulation tools and delivery systems, several challenges remain unresolved, including inefficient delivery, lack of sustained expression, immunogenicity, toxicity, capacity limitations, genomic integration risks, and limited tissue specificity. This review provides an overview of the plasmid-based gene therapy techniques and delivery methods currently employed for monogenic diseases, highlighting the challenges they face and exploring potential strategies to overcome these barriers.<\/jats:p>","DOI":"10.3390\/pharmaceutics17010104","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T03:29:43Z","timestamp":1736825383000},"page":"104","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Plasmid Gene Therapy for Monogenic Disorders: Challenges and Perspectives"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0862-3321","authenticated-orcid":false,"given":"Marco A.","family":"Lu\u00eds","sequence":"first","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"},{"name":"RISE-Health, Faculty of Sciences, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"},{"name":"Departament of Chemistry, Faculty of Sciences, University of Beira Interior, Rua Marqu\u00eas de \u00c1vila e Bolama, 6201-001 Covilh\u00e3, Portugal"}]},{"given":"Marcelo A. D.","family":"Goes","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"},{"name":"RISE-Health, Faculty of Sciences, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"},{"name":"Departament of Chemistry, Faculty of Sciences, University of Beira Interior, Rua Marqu\u00eas de \u00c1vila e Bolama, 6201-001 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4041-1504","authenticated-orcid":false,"given":"F\u00e1tima Milhano","family":"Santos","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"},{"name":"RISE-Health, Faculty of Sciences, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"},{"name":"Fundaci\u00f3n Jim\u00e9nez D\u00edaz University Hospital Health Research Institute (IIS-FJD), Av. Reyes Cat\u00f3licos, 28040 Madrid, Spain"}]},{"given":"Joana","family":"Mesquita","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"},{"name":"RISE-Health, Faculty of Sciences, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"}]},{"given":"Paulo","family":"Tavares-Ratado","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"},{"name":"Department of Medical Sciences, Faculty of Health Sciences, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"},{"name":"Laboratory of Clinical Pathology, Sousa Martins Hospital, Unidade Local de Sa\u00fade (ULS) da Guarda, Av. Rainha D. Am\u00e9lia, 6300-749 Guarda, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0927-2331","authenticated-orcid":false,"given":"C\u00e2ndida Teixeira","family":"Tomaz","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"},{"name":"RISE-Health, Faculty of Sciences, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"},{"name":"Departament of Chemistry, Faculty of Sciences, University of Beira Interior, Rua Marqu\u00eas de \u00c1vila e Bolama, 6201-001 Covilh\u00e3, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/mt.2016.5","article-title":"Current Progress in Therapeutic Gene Editing for Monogenic Diseases","volume":"24","author":"Prakash","year":"2016","journal-title":"Mol. 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