药学学报, 2018, 53(4): 518-528
引用本文:
张燕宇, 高欣, 江宽, 太玲钰, 魏刚, 陆伟跃. 眼部疾病的基因治疗与递送策略[J]. 药学学报, 2018, 53(4): 518-528.
ZHANG Yan-yu, GAO Xin, JIANG Kuan, TAI Ling-yu, WEI Gang, LU Wei-yue. Gene therapy and delivery strategies for ocular diseases[J]. Acta Pharmaceutica Sinica, 2018, 53(4): 518-528.

眼部疾病的基因治疗与递送策略
张燕宇, 高欣, 江宽, 太玲钰, 魏刚, 陆伟跃
复旦大学药学院, 教育部智能化递药重点实验室, 上海 201203
摘要:
眼睛独特的生理构造使其在基因治疗方面彰显出明显的优势。近年来,越来越多治疗眼部疾病的基因药物进入临床试验,其中大部分是以腺相关病毒作为递送载体,通过局部注射途径给药,存在一定的风险。针对各种眼部疾病,传统的无创治疗手段如眼表滴入或全身给药虽能够达到一定的治疗效果,但是对于眼内和眼后段疾病,即使小分子药物也难以到达,这使得对基因药物眼部递送策略的研究迫在眉睫。为了更好地了解基因治疗眼部疾病的最新热点,本文介绍了相关的疾病与基因药物,总结了眼内基因递送的途径与吸收屏障,并侧重介绍了近年来报道的基因递送策略。克服眼部的吸收屏障并降低给药的潜在风险,有望为眼部基因治疗的临床应用带来曙光。
关键词:    基因治疗      眼部给药      病毒载体      非病毒载体      基因编辑     
Gene therapy and delivery strategies for ocular diseases
ZHANG Yan-yu, GAO Xin, JIANG Kuan, TAI Ling-yu, WEI Gang, LU Wei-yue
Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, China
Abstract:
Gene therapy has obvious advantages in the treatment of ocular diseases due to the unique structure of the eye. In recent years, there are more and more therapeutic gene-based drugs for ophthalmic application in clinical trials. Most of the delivery vectors are adeno-associated virus and administered via intraocular injection, which has potential risks. Traditional remedies, such as topical instillationor systemic administration, have limited therapeutic effects on the diseases in the posterior segment of the eye, where the chemical drugs are hard to reach. This makes the research of new strategies for gene drug delivery extremely urgent. For better understanding of the latest hot topics of ocular gene therapy, this article is prepared to introduce application of gene therapy to the typical ocular diseases and the corresponding gene-based medicines. The absorption routes for gene delivery into eyes and existing barriers are summarized. Finally, the gene delivery strategies are highlighted. The clinical application of ocular gene therapy will be boosted by overcoming the absorbing barriers and reducing the potential pitfalls.
Key words:    gene therapy    oculardrug delivery    viral vector    non-viral vector    gene editing   
收稿日期: 2017-09-09
DOI: 10.16438/j.0513-4870.2017-0890
基金项目: 国家自然科学基金资助项目(81573358,81690263).
通讯作者: 魏刚,Tel:86-21-51980091,Fax:86-21-51980090,E-mail:weigang@shmu.edu.cn
Email: weigang@shmu.edu.cn
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