Targeted deletion of cellular DNA sequences

Disclosed herein are methods and compositions for targeted deletion of double-stranded DNA. The compositions include fusion proteins comprising a cleavage domain (or cleavage half-domain) and an engineered zinc finger domain， and polynucleotides encoding same. Methods for targeted deletion include introduction of such fusion proteins， or polynucleotides encoding same， into a cell such that two targeted cleavage events occur. Subsequent cellular repair mechanisms result in deletion of sequences between the two cleavage sites.

本公开提供了用于双链DNA（double-stranded DNA）靶向缺失的方法与组合物。所述组合物包含两类组分：一类为融合蛋白（fusion protein），其由剪切结构域（cleavage domain，或剪切半结构域（cleavage half-domain））与工程化锌指结构域（engineered zinc finger domain）组成；另一类为编码上述融合蛋白的多核苷酸（polynucleotide）。靶向缺失的方法包括将上述融合蛋白或其编码的多核苷酸导入细胞，以触发两次靶向剪切事件。后续的细胞修复机制将导致两个剪切位点之间的序列发生缺失。