Cholesterol-Conjugated SiRNA Accumulates In The Different Hematopoietic And Lymphoid Cells

Small interfering RNA (siRNA)based drugs for overcoming multiple drug resistance ofhematological malignanciescould solve the problem of poor response to the chemotherapy and hight relapse rate. The mainfactor that significantly limitsbiomedical application of siRNA is inefficient delivery to target cellsand tissues. The attachment of siRNA to molecules, which enter into the cell by natural transportmechanisms, can improvecellular uptake of siRNA. In current study the carrier-freecellular uptake of siRNA containigcholesterol residues conjugated to the 5’-end of the sense strand via oligomethylene linker of variouslength (here and after Ch-siRNA) was explored. The data demonstrate that cholesterol residue increase the accumulation of siRNA in all tested cell lines and the primary cells. The efficiency of Ch-siRNA accumulation in K562 cells depends greatly on the leangth of the linker connecting cholesterol and siRNA: Ch-siRNAs with linkerof 10 - 12 methylene units accumulate the most efficiently in this cells. It was found that Ch-siRNA effectively accumulates inMOLT-3 (acute lymphoblastic leukemia, ALL), HL-60 (acute myelogenous leukemia, AML), K562 (chronic myelogenous leukemia CML) and primary peripheral blood mononuclear cells (PBMC) from patient with non-Hodgkin lymphoma (NHL) or healthy donorresulting in near 100% of transfected cell whenused at 1 mM concentration.