CAJ | 학술논문

Leber先天性黑矇(LCA)是严重的遗传性视神经及视网膜疾病,可导致儿童先天性双眼盲.近十余年来,随着分子遗传学研究的进展及基因治疗技术的不断改进,腺相关病毒(AAV)载体介导的LCAⅡ基因治疗的基础研究工作为临床前研究奠定了良好的基础,这些研究包括相关基因载体的玻璃体腔内注射和视网膜下腔注射,研究指标包括治疗后受试眼视功能的改变及治疗的安全性,后者包括受试动物的免疫反应、眼组织的组织病理学改变、眼部并发症及载体的生物学分布.基于这些临床前基础研究的结果,目前LCAⅡ基因治疗的初步临床试验也取得了令人振奋的结果,这些结果一方面为LCA的治疗带来了希望,同时也为其他遗传性视网膜疾病的基因治疗积累了经验.就LCAⅡ型临床前基因治疗的基础研究现状进行综述.
Leber선천성흑몽(LCA)시엄중적유전성시신경급시망막질병,가도치인동선천성쌍안맹.근십여년래,수착분자유전학연구적진전급기인치료기술적불단개진,선상관병독(AAV)재체개도적LCAⅡ기인치료적기출연구공작위림상전연구전정료량호적기출,저사연구포괄상관기인재체적파리체강내주사화시망막하강주사,연구지표포괄치료후수시안시공능적개변급치료적안전성,후자포괄수시동물적면역반응、안조직적조직병이학개변、안부병발증급재체적생물학분포.기우저사림상전기출연구적결과,목전LCAⅡ기인치료적초보림상시험야취득료령인진강적결과,저사결과일방면위LCA적치료대래료희망,동시야위기타유전성시망막질병적기인치료적루료경험.취LCAⅡ형림상전기인치료적기출연구현상진행종술.
Leber congenital amaurosis (LCA) is extremely severe hereditary retinal dystrophy,because it leads to congenital bilateral blindness in early childhood.With the development of molecular genetics and the therapeutic gene replacement technology,gene therapy clinical trials have obtained exciting results on the basis of relatively satisfied with preliminary clinical experimental results by adeno-associated virus (AAV) vector-mediated gene therapy in the past decade.These researching methods include intravitreal injection and subretinal space injection of gene vector,and the investigating indexes include evaluations of visual function and safety,such as immune reaction of the animals,ocular histopathological change,complications and bio-distribution of gene sequence.The preliminary success of the LCAⅡ Ⅱ gene therapy will give some clues to the other inherited retinal diseases.This review focuses on the present status of pre-clinical animal experiments of its gene therapy.