Artificially-manipulated neovascularization regulatory system

A method for treating an ocular neovascularization disease, comprising introducing or administering a composition to a subject having the ocular neovascularization disease wherein the ocular neovascularization disease is selected from the group consisting of diabetic retinopathy, macular degeneration, ischemic retinopathy, and retinopathy of prematurity,

• in which the composition comprises
• i) an editor protein or a nucleic acid encoding the editor protein, wherein the editor protein is Campylobacter jejuni Cas9 protein;
• and
• ii) a guide nucleic acid capable of targeting a target sequence, or a nucleic acid encoding the guide nucleic acid,
• wherein the target sequence is selected from SEQ ID NOs:
• 18, 19, 20, 26, and 29 which is present within a HIF1A gene on a genome in the cell and a proto-spacer-adjacent motif (PAM), wherein the PAM sequence is contiguous 8 nucleotide sequence that exists in the genome in the 3′ direction of the target sequence, which is NNNNRYAC, wherein each N is independently A, T, C or G, R is A or G, and Y is C or T,
• wherein the guide nucleic acid comprises
• a guide domain capable of targeting the target sequence, and a sequence in which a first complementary domain, a linker domain, a second complementary domain, a proximal domain and a tail domain are linked in a direction of 5′ to 3′,
• wherein the guide nucleic acid and the editor protein form a complex and induces a double strand break in nucleic acid of the HIF1A gene,
• wherein the composition is formed in an adeno-associated virus (AAV) vector system, and
• wherein the composition induces an indel mutation by NHEJ (Non-homologous end joining) mechanism within the HIF1A gene in the cell.