AAV-mediated human CNGB3 restores cone function in an all-cone mouse model of CNGB3 achromatopsia

• 来源期刊: 生物医学研究杂志（英文版）
• 学科: 医学
• 年，卷（期）: 2020,（2）
• 页码范围: 114-121
• 页数: 8页
• 分类号: R774.1
• 语种: 英文

摘要

Complete congenital achromatopsia is a devastating hereditary visual disorder.Mutations in the CNGB3 gene account for more than 50％ of all known cases of achromatopsia.This work investigated the efficiency of subretinal (SR) delivered AAV8 (Y447,733F) vector containing a human PR2.1 promoter and a human CNGB3 cDNA in Cngb3-/-/Nrl-/-mice.The Cngb3-/-/Nrl-/-mouse was a cone-dominant model with Cngb3 channel deficiency,which partially mimicked the all-cone foveal structure of human achromatopsia with CNGB3 mutations.Following SR delivery of the vector,AAV-mediated CNGB3 expression restored cone function which was assessed by the restoration of the cone-mediated electroretinogram (ERG) and immunohistochemistry.This therapeutic rescue resulted in long-term improvement of retinal function with the restoration of cone ERG amplitude.This study demonstrated an AAV-mediated gene therapy in a cone-dominant mouse model using a human gene construct and provided the potential to be utilized in clinical trials.