Investigation of LL-37-mediated siRNA transfection

摘要

RNA interference is not only an important tool for studying protein function; it also holds many promises for the treatment of a variety of diseases in which the function of unwanted proteins needs to be suppressed. For small interfering RNA (siRNA) to be used as a therapeutic agent, the biggest hurdle is to find the right delivery agent that is both nontoxic to the cells and efficient in delivery. Synthetic and natural peptides from a variety of organisms have been investigated for this purpose. However, there is still no agent or formulation that has been approved for siRNA delivery. Antimicrobial peptide LL-37 has been reported to deliver negatively charged cargo molecules like DNA into the mammalian cells. Since it is nontoxic and nonimmunogenic, and it has the ability to penetrate through mammalian cells in complex with negatively charged molecules, LL-37 peptide appears to make an ideal delivery agent for siRNA therapy. In this report, LL-37/siRNA complexes have been characterized and LL-37-mediated transfection has been investigated in vitro. The results show that the efficiency of delivery was dependent on the cell type, and for LL-37 to be used as a siRNA delivery agent, conditions have to be optimized for each target tissue type.