improved method for synthesis of low molecular weight protamine–sirna conjugate
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ID: 221438
2018
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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 in vivo 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 via 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.
| Reference Key |
yu2018actaimproved
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|---|---|
| Authors | ;Zhili Yu;Junxiao Ye;Xing Pei;Lu Sun;Ergang Liu;Jianxin Wang;Yongzhuo Huang;Seung Jin Lee;Huining He |
| Journal | energy policy |
| Year | 2018 |
| DOI |
10.1016/j.apsb.2017.11.011
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