title: Minicircle DNA vectors for gene therapy: advances and applications.
abstract: BACKGROUND
  Nucleic-acid-based biopharmaceuticals enclose a remarkable potential for treating debilitating or life-threatening diseases that currently remain incurable. This promising area of research envisages the creation of state-of-the-art DNA vaccines, pluripotent cells or gene-based therapies, which can be used to overcome current issues. To achieve this goal, DNA minicircles are emerging as ideal nonviral vectors due to their safety and persistent transgene expression in either quiescent or actively dividing cells.
  
  
  METHODS
  This review focuses on the characteristics of minicircle DNA (mcDNA) technology and the current advances in their production. The possible modifications to further improve minicircle efficacy are also emphasized and discussed in light of recent advances. As a final point, the main therapeutic applications of mcDNA are summarized, with a special focus on pluripotent stem cells production and cancer therapy.
  
  
  CONCLUSIONS
  Achieving in-target and persistent transgene expression is a challenging issue that is of critical importance for a successful therapeutic outcome. The use of miniaturized mcDNA cassettes with additional modifications that increase and prolong expression may contribute to an improved generation of biopharmaceuticals. The unique features of mcDNA render it an attractive alternative to overcome current technical issues and to bridge the significant gap that exists between basic research and clinical applications.
authors.affiliation: University of Beira Interior, CICS-UBI - Health Sciences Research Center , Av. Infante D. Henrique, 6200-506, Covilhã , Portugal +351 275 329 002, +351 275 329 055 ; +351 275 329 099 ; fani.sousa@fcsaude.ubi.pt ; icorreia@ubi.pt.
authors.forename: Vítor
authors.initials: V
authors.lastname: Gaspar
authors.forename: Duarte
authors.initials: D
authors.lastname: de Melo-Diogo
authors.forename: Elisabete
authors.initials: E
authors.lastname: Costa
authors.forename: André
authors.initials: A
authors.lastname: Moreira
authors.forename: João
authors.initials: J
authors.lastname: Queiroz
authors.forename: Chantal
authors.initials: C
authors.lastname: Pichon
authors.forename: Ilídio
authors.initials: I
authors.lastname: Correia
authors.forename: Fani
authors.initials: F
authors.lastname: Sousa
mesh_terms: D000818:Animals; D001702:Biopharmaceutics / Q000639:trends; D004270:DNA, Circular / Q000008:administration & dosage* / Q000235:genetics*; D018014:Gene Transfer Techniques / Q000639:trends; D015316:Genetic Therapy / Q000379:methods / Q000639:trends*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D006801:Humans; D019076:Transgenes / Q000235:genetics
chemical_list: D004270:DNA, Circular
keywords: DNA-vaccines; cell therapy; gene therapy; minicircle DNA; transgene expression