Development of ocular gene therapy and chromosome therapy in Japan

基因治疗是目前尚无有效治疗方法的各种疾病的最具创新性和潜在有效的治疗方法，然而，在日本临床应用之前还有许多问题有待解决。这是因为基因治疗技术受到严格的专利保护，其中大部分由非日本公司或个人拥有。考虑到基因治疗对未来医学的社会经济影响，我们有必要在日本开发原创的基因治疗技术。1）猴免疫缺陷病毒（Simian immunodeficiency virus，SIV）载体介导的视网膜变性基因治疗：由日本DYNAVEC公司开发的SIV载体能够将目的基因长时间转移到染色体中。本研究利用SIV载体将GFP基因注射到猴眼内，使GFP在猴眼内稳定表达长达12个月，且无形态和功能损伤。目前，bFGF、PEDF等神经保护性基因转移的效果正在研究中。2）超声（US）介导的基因转移：目前超声已被医学界广泛接受，其安全性已得到证实。因此，我们开发了一种US介导的眼部基因转移。将GFP cDNA注射到角膜中，然后暴露于US和微泡。结果，在没有组织损伤的情况下实现了二维样基因转移。3）新的手术技术：基因转移的安全操作是进行人类基因治疗的关键问题。为此，我们研制了一种曲安奈德辅助的玻璃体切割术，降低了手术并发症的发生率。这将为在日本建立一种新的眼部基因治疗方法做出巨大贡献。

Gene therapy is the most innovative and potentially effective therapy for various diseases for which no effective therapy exists, however, there are many problems to be solved before clinical application in Japan. It is because the technology of gene therapy is strictly protected by patents, most of which are owned by non-Japanese companies or individuals. Thinking of socio-economical impact of gene therapy in future medicine, it is necessary for us to develop an original gene therapy technology in Japan. Therefore, we performed the following esperiments.1)Simian immuno-deficiency virus(SIV)-vector mediated gene therapy for retinal degeneration : SIV-vector which was developed by DYNAVEC (Japan) can transfer genes of interest into a choromosome for a long period. In this study, GFP-gene was injected into the monkey eyes using SIV-vector, resulting in stable expression of GFP for as long as 12 months without morphological and functional damages. No systemic adverse effect was found. Now, the effect of neuro-protective gene transfer such as bFGF and PEDF is under investigation.2)Ultrasound(US)-mediated gene transfer : US is widely accepted to the current medical fields and its safeness has been established. Thus, we developed an US-mediated gene transfer to eyes. GFP cDNA was injected into the cornea followed by exposure to US and micorbubbles. As a result, 2-dimension-like gene transfer was achieved with no tissue damage. This method is under patent proposal.3)New surgical technology : Safety maneuver to gene transfer is a key issue to perform human gene therapy. For that, we develop a triamcinolone-assisted vitrectomy, which decreased the incidence of surgical complication s.All of the above results are original and free from the foreign patent restriction. This will make a great contribution to establish a new ocular gene therapy in Japan.