Reducible Dimeric Conjugates of Small Internally Segment Interfering RNA for Efficient Gene Silencing.
The condensation of nucleic acids into compact nanoparticles with cationic carriers is a powerful tool for translocating exogenous nucleic acids into cells. To date, most efforts have been focused on the development of novel gene carriers for safe and efficient gene delivery. However, small interfering RNA (siRNA) is generally not strongly associated with cationic carriers due to its stiff structure and low spatial charge density. To overcome this limitation, this work introduces a well-defined dimeric conjugate of small internally segment interfering RNA (sisiRNA) linked via a disulfide bond for enhanced cellular uptake and gene silencing. Dimeric sisiRNA is synthesized through oxidizing two monomeric sisiRNA molecules, each of which consists of a sense strand carrying a nick and an antisense strand modified with a thiol group at the 3'-end. The nick in the sense strand enables the dimeric sisiRNA to be more effectively condensed into nanosized complexes due to the increased structural flexibility, which results in a higher gene silencing efficiency compared with the dimeric siRNA containing the intact sense strands. The results indicate that the discontinuity of the sense strands is a simple method of adding more flexibility to various siRNA-based nanostructures for enhanced gene silencing.
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
Cheol Am
CA
Hong
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea. yoonsung@kaist.ac.kr.|Department of Materials Science and Engineering, and KAIST Institutes for NanoCentury and Health Science and Technology, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea. yoonsung@kaist.ac.kr.
Yoon Sung
YS
Nam
D016503:Drug Delivery Systems / Q000379:methods*; D020868:Gene Silencing / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D049329:Nanostructures / Q000737:chemistry / Q000627:therapeutic use; D034741:RNA, Small Interfering / Q000737:chemistry / Q000494:pharmacology
D034741:RNA, Small Interfering
chain flexibility; gene silencing; polymeric condensation; siRNA; siRNA nanostructures