Figure 1.

Correction of the sickle mutation in long-term xenografted hematopoietic cells

(A) Schematic depicting the β-globin gene (HBB) with the targeted region enlarged. Sequence shown in black is the sickle allele. The G10 guide RNA (red line) targets Cas9 cleavage to a site near the sickle mutation. The 168-base single-stranded DNA oligonucleotide donor induces sequence changes shown in red. HDR tract conversion proceeds from the Cas9 cleavage site (red arrow), alters the PAM motif to prevent cleavage of the edited allele, but does not always extend to the site of the sickle mutation.

(B) Schematic outlining the large-scale xenografting experiment, and analysis of the engrafted cells.