Designing of RNA Molecule Translating for Activitable Melit-tin as Selective Targeting of Leishmania Infected Cells

Abstract

Background: Leishmaniasis is characterized by strong inflammatory responses with high levels of inflammatory cytokines that induce microRNA 21 and matrix metalloproteinases. Melittin has inhibitory effects on proliferation of various cells via induction of apoptosis. Melittin can be integrated in cell membranes and induce apoptosis. Thus, designation of biomolecules for the selective destroy of the infected cells is a treatment option. One approach is the precise engineering of constructs for the selective expression of melittin in the infected cells. Methods: For this aim we designed a construct composing melittin nucleotide sequence and nucleotide sequence coding for polyanionic peptide function inhibitory element to further guarantee the selective function of melittin in inflamed tissues and infected cells, were included in a construct as melittin inhibitor via matrix metalloproteinase degradable linker. Results: Reverse complementary sequences were designed so melittin sequences for the selective targeting of Leishmania could be expressed in infected cells using cell microRNA machinery. Conclusion: Translation machinery in infected cells with increased miR-21 could translate melittin, MMP linker and polyanionic inhibitor through a non-canonical pathway. Then, the MMP linker is degraded and selective killing of Leishmania infected cells would happen.

Keywords

• RNA design
• Leishmania spp.;
• Melittin;
• miR-21;
• microRNA machinery