Provided herein are improved rAAV (e.g., rAAV2, rAAVrh8R, etc.) for enhanced gene therapy of ocular disorders or CNS disorders wherein the rAAV comprise one or more substitutions of amino acids that interact with heparan sulfate proteoglycan. The invention provides methods for improved transduction of retinal cells and methods for treating ocular diseases with improved compositions of rAAV particles. Further provided herein are improved recombinant adeno-associated virus (rAAV) (e.g., rAAV2, rAAVrh8R, etc.) for enhanced gene therapy of disorders of the CNS. The invention provides methods for delivering the rAAV to the CNS, methods for treating disorders of the CNS with improved compositions of rAAV particles, and kits for delivering the rAAV to the CNS and/or treating a CNS disorder.本申請提供改進的rAAV(例如,rAAV2,rAAVrh8R等)用於眼部病症或CNS病症的增強的基因治療,其中該rAAV包含一個或多個與硫酸乙醯肝素蛋白多糖相互作用的胺基酸的取代。本發明提供用於視網膜細胞改進的轉導的方法和用於以rAAV顆粒的改進組成物治療眼部病症的方法。本申請還提供改進的重組腺相關病毒(rAAV)(例如,rAAV2、rAAVrh8R等)用於CNS的病症的增強的基因治療。本發明提供用於將rAAV遞送至CNS的方法,用於以rAAV顆粒的改進組成物治療CNS的病症的方法,和用於將rAAV遞送至CNS和/或治療CNS病症的套組。