Our results suggest that the single loop residue abasic substitution may represent a useful route for the design of antiproliferative G4-oligonucleotides, in particular taking into account that several G4 aptamers endowed with antiproliferative activity, binding different targets and therefore being involved in different cancer cell pathways, are characterized by loops containing a single residue, such as AS1411 and anti-STAT aptamer [26,38]. Here, SOAT1 is linked to cancer.