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Investigation of LL-37-mediated siRNA transfection

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. | Turkish Journal of Biology http://journals.tubitak.gov.tr/biology/ Research Article Turk J Biol (2013) 37: 426-432 © TÜBİTAK doi:10.3906/biy-1208-50 Investigation of LL-37-mediated siRNA transfection Mustafa YALÇINKAYA, Şahru YÜKSEL* Molecular Biology and Genetics Department, Center for Life Sciences and Technologies, Boğaziçi University, Bebek, İstanbul, Turkey Received: 23.08.2012 Accepted: 17.12.2012 Published Online: 30.07.2013 Printed: 26.08.2013 Abstract: 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. Key words: Antimicrobial peptide, LL-37, siRNA, shRNA, transfection, cell-penetrating peptides 1. Introduction RNA interference (RNAi) is a rapidly developing and evolving field holding many promises for laboratory and therapeutic applications. It was shown for the