Department of Dermatology, the First Affiliated Hospital of Jinan University, Guangzhou Overseas Chinese Hospital, Guangzhou 510630, China.
Charles Institute of Dermatology, University College Dublin, Dublin 4, Ireland.
Adv Drug Deliv Rev. 2021 Sep;176:113842. doi: 10.1016/j.addr.2021.113842. Epub 2021 Jul 20.
Non-viral gene therapy for hereditary skin diseases is an attractive prospect. However, research efforts dedicated to this area are rare. Taking advantage of the branched structural possibilities of polymeric vectors, we have developed a gene delivery platform for the treatment of an incurable monogenic skin disease - recessive dystrophic epidermolysis bullosa (RDEB) - based on highly branched poly(β-amino ester)s (HPAEs). The screening of HPAEs and optimization of therapeutic gene constructs, together with evaluation of the combined system for gene transfection, were comprehensively reviewed. The successful restoration of type VII collagen (C7) expression both in vitro and in vivo highlights HPAEs as a promising generation of polymeric vectors for RDEB gene therapy into the clinic. Considering that the treatment of patients with genetic cutaneous disorders, such as other subtypes of epidermolysis bullosa, pachyonychia congenita, ichthyosis and Netherton syndrome, remains challenging, the success of HPAEs in RDEB treatment indicates that the development of viable polymeric gene delivery vectors could potentially expedite the translation of gene therapy for these diseases from bench to bedside.
非病毒基因治疗遗传性皮肤疾病具有很大的吸引力。然而，这方面的研究工作却很少。利用聚合物载体的支化结构可能性，我们基于高度支化的聚（β-氨基酯）（HPAE）开发了一种用于治疗一种无法治愈的单基因皮肤疾病 - 隐性营养不良性大疱性表皮松解症（RDEB）的基因传递平台。对 HPAE 的筛选和治疗性基因构建体的优化，以及对基因转染联合系统的评估进行了全面综述。成功地在体外和体内恢复了 VII 型胶原蛋白（C7）的表达，这突出了 HPAE 作为一种有前途的聚合物载体，可将 RDEB 基因治疗应用于临床。考虑到对遗传性皮肤疾病患者的治疗，如其他亚型的大疱性表皮松解症、先天性厚甲症、鱼鳞病和 Netherton 综合征，仍然具有挑战性，HPAE 在 RDEB 治疗中的成功表明，可行的聚合物基因传递载体的开发有可能加速这些疾病的基因治疗从实验室到临床的转化。
