Structure–activity relationship of a guanine-free oligodeoxynucleotide as immunopotent inhibitor

Structure, mechanism and therapeutic utility of immunosuppressive oligonucleotides

“…In a murine model of acute lung inflammation, MS19 significantly inhibited weight loss and hemorrhage, reduced intra-alveolar edema and lessened the accumulation of neutrophils in the lungs [81,88,90]. H154 inhibited the pulmonary inflammation induced by the delivery of immunostimulatory bacterial products (such as CpG DNA) into the lungs of mice was evaluated [91].…”

“…Similarly, a 5-mer poly-G is suppressive only when incorporated into a longer ODN [71]. Studies of various classes of Sup ODN indicate that sequences shorter than 11 nucleotides have little suppressive activity while those longer than 24 nucleotides gain little additional function [8,62,72,77,78,90]. This pattern was also observed in studies of TTAGGG multimers: suppressive activity increased as more motifs were added but only to a point, with ODN containing 5 repeats being no more active than those with 4 TTAGGG repeats [1,90].…”

An immune regulatory CCT repeat containing oligodeoxynucleotide capable of causing hair loss in male mice

“…Overall, in our previous study, CCT ODN displayed immunosuppressive activities by selectively downregulating TLR7/9-mediated immune responses, 1 –3 but its target and signal pathway were still unclear. In this study, CCT ODN-induced hair loss in male F1 mice and male Balb/c mice is likely through NKG2D + cells and IFN-γ, suggesting that it might play immunostimulatory activities in an individual with certain genetic background.…”

“…An ODN with CCT repeats (CCT ODN) has been previously demonstrated in our study to selectively downregulate TLR7/9-mediated innate immune responses. [1][2][3] To test whether the CCT ODN could treat autoimmune disease, we established a mouse model of lupus-like nephritis induced by injection of allogenic lymphocytes in F1 mice (female Balb/c mice  male C57BL/6 mice). 6 During the treatment with CCT ODN by i.p.…”

“…An oligodeoxynucleotide with CCT repeats (CCT ODN) has been found in our previous study to selectively downregulate Toll-like receptor 7/9 (TLR7/9)mediated immune responses in cultured immune cells in vitro and in mice, showing the characteristics of inhibitory ODNs (IN-ODNs). [1][2][3] The IN-ODNs with defined sequences have been demonstrated to inhibit innate immune response triggered by CpG ODNs, bacterial DNA, or cytosolic double stranded (ds) DNA. 4 Structurally, all of the IN-ODNs published contain G, 5 but the CCT ODN, in contrast, contains no G and could be classified as NO-G-IN-ODNs.…”