B7 Antisense Phosphorothioate Oligonucleotide's Design And Synthesisis And It's Effect On Rat Cardiac Allograft

Objective: To explore a new immune suppressor for inducing transplantation tolerance, appropriate antisense oligonucleotides of B7 was designed and a model of rat cardiac allgraft was established .Then antisense oligonucleotides of B7 was used as immune depressor to block the mRNA of B7 at gene level. The survival time of the transplanted hearts was observed.Methods : According to the design principle of antisense oligonucleotide, the antisense oligonucleotide of B7 was designed, synthesized, and purified and then injected into the rat cardiac allograft model as immune depressor drugs. The survival of the cardiac allografts was observed and comparedwith other contrast groups.Result: The model of rats cardiac allograft was successfully established. The antisense phosphorothioate oligonucleotides were designed for aiming at origination area and termination area and the area containing GGGA segment ,in which the single chain was 20bps in length. Another random contrast sequence was also designed . The antisense phosphorothioate oligonucleotides were successfully synthesized by using DNA synthesize instruments, and purified by PAGE ,their quantity and purification were eligible. Only the phosphorothioate oligonucleotides aimed at the area containing GGGA segment had effect of prolonging the rat cardiac allograft survival time.Conclusion: The rat cardiac allograft model is steady, and its procedure was easily practised . The antisense phosphorothioate oligonucleotides aimed at the sequence containing GGGA segment is effective for anti-rejection, which indicates that the mRNA of B7 can be blocked by the oligonucleotides. In this study, a new approach through blocking costimulatory signal at gene level to induce immune tolerance is created.