KMID : 0578320100290050457
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Molecules and Cells 2010 Volume.29 No. 5 p.457 ~ p.462
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Leukemia-Specific siRNA Delivery by Immunonanoplexes Consisting of Anti-JL1 Minibody Conjugated to Oligo-9 Arg-Peptides
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Lee Yeon-Kyung
Kim Keun-Sik Kim Jung-Seok Baek Jin-Ee Jeong Hwa-Yeon Yoon Sang-Soon Jung Kyeong-Cheon Song Hyung-Geun Park Yong-Serk
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Abstract
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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 non-specific delivery. To solve these problems, we developed an anti-JL1 immunonanoplex (antibody-coupled nano-complex) 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 im-munonanoplexes were effectively targeted to JL1-positive cells (CEM) inoculated in the mouse bone marrow. These results suggest that the anti-JL1 immu-nonanoplex is a powerful siRNA delivery system for human leukemia therapies.
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KEYWORD
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9-arginine peptide, anti-JL1 minibody, immunonanoplex, leukemia therapy, siRNA
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