ABSTRACT
RNAi technology has aroused wide public interest due to its high efficiency and specificity to treat multiple types of diseases. However, the effective delivery of siRNA remains a challenge due to its large molecular weight and strong anionic charge. Considering their remarkable functions and features that are often desired in drug delivery carriers, biomimetic systems for siRNA delivery become an effective and promising strategy. Based on this, covalent attachment of synthetic cell penetrating peptides (CPP) to siRNA has become of great interest. We developed a monomeric covalent conjugate of low molecular weight protamine (LMWP, a well-established CPP) and siRNA a cytosol-cleavable disulfide linkage using PEG as a crosslinker. Results showed that the conjugates didn't generate coagulation, and exhibited much better RNAi potency and intracellular delivery compared with the conventional charge-complexed CPP/siRNA aggregates. Three different synthetic and purification methods were compared in order to optimize synthesis efficiency and product yield. The methodology using hetero-bifunctional NHS-PEG-OPSS as a crosslinker to synthesize LMWP-siRNA simplified the synthesis and purification process and produced the highest yield. These results pave the way towards siRNA biomimetic delivery and future clinical translation.
ABSTRACT
The Pareto effect generated in use of journal articles covered in Wiley Online Library ( WOL) , a full-text database developed by China Pharmaceutical University, was analyzed, which showed that the number of WOL-covered source journals in ACIE, SSCI, A & HCI, the number of full-text journals that published SCI-covered papers of our university, the key and strong subjects of our university were the leading factors of Pareto effect gener-ated in use of WOL, studies on Pareto effect are thus of importance for the library in its development of literature resources, data information service and subject service.