부산대학교 도서관

Delivery of siRNAs to blood cells is one of the most difficult tasks since there are no efficient and nontoxic methods of delivering nucleic acids to these cells in vivo. Conjugation of siRNAs with targeting or lipophilic transport molecules is one of the most promising approaches to solving this problem, since it can provide efficient accumulation without toxic side effects. Therefore, in this work, we conjugated an siRNA molecule with lipophilic molecules for its delivery to PBMC (primary blood mononuclear cells) and whole blood cells. We showed that among the studied molecules, cholesterol is the most promising agent for this purpose. Further screening of conjugates with respect to the length of the linker connecting the siRNA and cholesterol showed that a linker containing six carbon atoms is optimal for the most efficient delivery of the siRNA into human cells in experiments in whole blood. The selected siRNA–cholesterol conjugate also efficiently accumulated in mouse blood cells and splenocytes upon intravenous injection. [ABSTRACT FROM AUTHOR]