In summary, using the Dmoc ODN synthesis method, we were able to synthesize sensitive ODNs containing the 6acA, 2acG, and 4mcC, as well as multiple 4acC modifications without any sequence limitations. The 4acC modification is highly sensitive, and therefore the ability of the Dmoc method to incorporate four of it into one ODN sequence is remarkable. The 6acA, 2acG and 4mcC modifications have not been found in nature. However, they may behave similarly as 4acC and ac4C in terms of benefits to DNA and RNA duplex stability, and may found applications such as antisense, RNAi, CRISPR, and mRNA therapeutics. We expect that the demonstration of their incorporation into ODNs in the present work will facilitate projects aimed at studying their biophysical properties and potentials for therapeutic applications.