Introduction The replacement of natural phosphodiester (PO) bonds in DNA or RNA by artificial internucleoside linkages can generate remarkable biomimetic oligonucleotides (ONs) with applications as therapeutics,(1) xenobiotic genetic polymers,(2−4) aptamers,(3,5−7) and synthetic genes.(8−10) Biological integrity and favorable biophysical properties are critical, and good hybridization properties, mismatch discrimination, and compatibility with certain enzymes (e.g., RNase H) play crucial...