Leukemia-specific siRNA delivery by immunonanoplexes consisting of anti-JL1 minibody conjugated to oligo-9 Arg-peptides

• Published in: Molecules and cells 2010, 29(5), , pp.457-462
• Main Authors: Lee, Y.K., Yonsei University, Wonju, Republic of Korea, Kim, K.S., Youngdong University, Youngdong, Republic of Korea, Kim, J.S., Yonsei University, Wonju, Republic of Korea, Baek, J.E., Yonsei University, Wonju, Republic of Korea, Park, S.I., Yonsei University, Wonju, Republic of Korea, Jeong, H.Y., Yonsei University, Wonju, Republic of Korea, Yoon, S.S., Dinona Inc., Iksan, Republic of Korea, Jung, K.C., Dinona Inc., Iksan, Republic of Korea, Song, H.G., Dinona Inc., Iksan, Republic of Korea, Park, Y.S., Yonsei University, Wonju, Republic of Korea
• Format: Article
• Language: English
• Subjects: 9-arginine peptide; Animals; anti-JL1 minibody; Antibodies, Monoclonal - genetics; Antibodies, Monoclonal - metabolism; Antigens, Differentiation, T-Lymphocyte - immunology; ARN; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Cell Biology; Female; Genetic Therapy; Humans; immunonanoplex; Jurkat Cells; leukemia therapy; Leukemia, T-Cell - genetics; Leukemia, T-Cell - immunology; Leukemia, T-Cell - metabolism; Leukemia, T-Cell - therapy; Life Sciences; Mice; Mice, SCID; Microscopy, Confocal; Neoplasm Transplantation; Peptide Fragments - genetics; Peptide Fragments - immunology; Peptide Fragments - metabolism; Protein Engineering; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - pharmacology; RNA; RNA, Small Interfering - genetics; siRNA; 생물학
• ISSN: 1016-8478; 0219-1032
• DOI: 10.1007/s10059-010-0056-5

Targeted mRNA degradation by short interfering RNAs (siRNAs) offers a great potential to treat cancers. siRNA therapeutics for leukemias are, however, hindered by poor intracellular uptake, limited blood stability and nonspecific delivery. To solve these problems, we developed an anti-JL1 immunonanoplex (antibody-coupled nanocomplex) for siRNA delivery using anti-JL1 minibody (leukemia cell-specific minibody) conjugated to oligo-9-Arg peptide (9R) for effective siRNA delivery to leukemic cells. The anti-JL1 immunonanoplexes were able to deliver siRNA specifically to leukemic cells (CEM and Jurkat), but not to control cancer cells (H9). According to FACS and confocal microscopic analysis, siRNAs delivered by immunonanoplex particles were rapidly taken up by the JL1-positive cancer cells in 2 h. Furthermore, we showed that the anti-JL1 immunonanoplexes were effectively targeted to JL1-positive cells (CEM) inoculated in the mouse bone marrow. These results suggest that the anti-JL1 immunonanoplex is a powerful siRNA delivery system for human leukemia therapies.