Genome Editing of Beta-Globin Gene Cluster Repressive Elements for Beta-ThalassemiaDescription of Major Goals
Specific Aim 1. Utilize a custom pooled CRISPR guide RNA library to perform high-resolution mutagenesis to determine minimal non-coding sequences at the B-globin gene cluster necessary for HbF repression. Specific Aim 2. Determine efficiency and specificity of genome editing human HSOCs by measuring rate of on-and off-target editing and impact on HbF level and henatopolesis.