Figure 4.

Two main approaches to block methylated DNA repair by targeting the MGMT protein. TMZ can add methyl to the guanine on the DNA molecule (form as 06-meG), which then induce DNA cross-linking. MGMT protein can repair DNA damage by binding and transferring the methyl on it. Low molecular weight O⁶-meG analogs, like O⁶-BG and O⁶-BTG, are used as pseudosubstrates to bind MGMT protein and reduce the methyl transfer activity. Specific miRNA/ liposome complexes which interact with MGMT 3'UTR then inhibit the MGMT mRNA translation process (RNAi). The proliferated oncolytic virus in a host can inhibit the host's MGMT promoter's activation, by means of the E1A binding to the p300.