Gaspar Vítor, de Melo-Diogo Duarte, Costa Elisabete, Moreira André, Queiroz João, Pichon Chantal, Correia Ilídio, Sousa Fani
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 ;
Expert Opin Biol Ther. 2015 Mar;15(3):353-79. doi: 10.1517/14712598.2015.996544. Epub 2014 Dec 24.
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.
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.
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.
基于核酸的生物制药在治疗目前仍无法治愈的衰弱性或危及生命的疾病方面具有巨大潜力。这一充满前景的研究领域设想开发出最先进的DNA疫苗、多能细胞或基于基因的疗法，以克服当前的问题。为实现这一目标，DNA微环正作为理想的非病毒载体崭露头角，因为它们在静止或活跃分裂的细胞中具有安全性和持续的转基因表达。
本综述重点关注微环DNA（mcDNA）技术的特点及其生产的当前进展。还根据最近的进展强调并讨论了为进一步提高微环功效而可能进行的修饰。最后，总结了mcDNA的主要治疗应用，特别关注多能干细胞的产生和癌症治疗。
实现靶向和持续的转基因表达是一个具有挑战性的问题，对于成功的治疗结果至关重要。使用经过额外修饰以增加和延长表达的小型化mcDNA盒可能有助于改进生物制药的生产。mcDNA的独特特性使其成为克服当前技术问题以及弥合基础研究与临床应用之间巨大差距的有吸引力的替代方案。
