Targeted In Situ Gene Correction of Dysfunctional APOE Alleles to Produce Atheroprotective Plasma ApoE3 Protein

Figure 1

Structure of the human APOE gene. The APOE gene has 4 exons, comprising 44, 66, 193, and 860 nucleotides, with over 80% of the protein coded for by exon 4. Exon 1 contains 5′ untranslated sequence, while the translated sequence in exon 2 codes for most of the 18 residue signal peptide. As indicated, exon 4 contains the two common disease-associated SNPs: a T→C point mutation produces ApoE4 (Cys112Arg), while C→T mutation gives ApoE2 (Arg158Cys). The wild-type sequence is ApoE3 (Cys112, Arg158). Also shown in the lower part of the figure is the positively charged arginine- and lysine-rich 𝛼-helical segment (residues 134–150) which recognizes the LDL receptor.