Fig. 5. Chemical modifications to enhance nuclease resistance.

Various chemical modifications have been demonstrated to increase the nuclease resistance of DNA structures. These approaches include ligation of strand termini¹⁰⁵ (part a); crosslinking of component strands by click chemistry¹¹⁴ (part b); crosslinking of strands through the formation of a thymidine dimer under ultraviolet (UV) irradiation¹¹⁵ (part c); the introduction of terminal functional groups, such as hexaethylene glycol and hexanediol¹¹³ (part d); the use of l-DNA¹¹⁷ (part e); and the use of unnatural base pairs (where 5-Me-isoC is 5-methyl-isocytidine; part f)¹¹⁸.