Sheu Eric, Rothman Stephen, German Michael, Wang Xuegong, Finer Mitchell, McMahon Beth M
Genteric Inc, 1650 Harbor Bay Parkway, Alameda, CA 94502, USA.
Curr Opin Mol Ther. 2003 Aug;5(4):420-7.
Gene delivery represents a revolutionary therapeutic approach with the potential for sustained protein production by the human body, leading to a convenient and effective method for systemic delivery of protein drugs. In this review, advantages of an orally administered DNA formulation, Gene Pill, are presented. Unlike previously described DNA delivery approaches, the Gene Pill enables DNA delivery in a non-invasive manner, leading to the secretion of therapeutic proteins into a patient's blood, supplanting the need for injection of therapeutic protein products. The Gene Pill also has potential for the development of oral DNA vaccination through expression of protein antigens in the gut lymphoid tissue. This approach limits the biodistribution of the delivered DNA to the gut and retains all of the safety advantages of non-viral gene delivery, including repeat dosing. Development of an oral DNA formulation involves overcoming several challenges, including depurination by low pH in the stomach, enzymatic degradation by DNases in the gut, crossing the physical barrier imposed by the mucus layer, cell entry, intracellular trafficking and nuclear uptake. The advantages of the Gene Pill technology, as well as challenges for its development, are presented in this review.
基因递送是一种革命性的治疗方法，具有让人体持续产生蛋白质的潜力，从而为蛋白质药物的全身递送提供了一种便捷有效的方法。在本综述中，介绍了口服DNA制剂“基因药丸”的优势。与先前描述的DNA递送方法不同，“基因药丸”能够以非侵入性方式递送DNA，使治疗性蛋白质分泌到患者血液中，从而无需注射治疗性蛋白质产品。“基因药丸”还具有通过在肠道淋巴组织中表达蛋白质抗原来开发口服DNA疫苗的潜力。这种方法将递送的DNA的生物分布限制在肠道，并保留了非病毒基因递送的所有安全优势，包括重复给药。开发口服DNA制剂涉及克服几个挑战，包括胃中低pH值导致的脱嘌呤、肠道中DNase的酶促降解、穿过黏液层造成的物理屏障、细胞进入、细胞内运输和核摄取。本综述介绍了“基因药丸”技术的优势及其开发面临的挑战。
