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Mol. Cells 2010; 29(5): 457-462

Published online May 31, 2010

https://doi.org/10.1007/s10059-010-0056-5

© The Korean Society for Molecular and Cellular Biology

Leukemia-Specific siRNA Delivery by Immunonanoplexes Consisting of Anti-JL1 Minibody Conjugated to Oligo-9 Arg-Peptides

Yeon Kyung Lee, Keun Sik Kim1, Jung Seok Kim, Jin Ee Baek, Sang Il Park, Hwa Yeon Jeong,Sang Soon Yoon2, Kyeong Cheon Jung2,3, Hyung Geun Song2,4, and Yong Serk Park*

Department of Biomedical Laboratory Science, Yonsei University, Wonju 220-710, Korea, 1Department of Biomedical Sciences, Youngdong University, Yeongdong 370-701, Korea, 2Department of Development and Manufacturing, Dinona Inc., Iksan 570-912, Korea, 3Department of Pathology, Seoul National University College of Medicine, Seoul 110-799, Korea, 4Department of Pathology, Chungbuk National University College of Medicine, Cheongju 361-763, Korea

Correspondence to : *Correspondence: parkys@yonsei.ac.kr

Received: September 25, 2010; Revised: December 29, 2010; Accepted: February 1, 2010

Abstract

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.

Keywords 9-arginine peptide, anti-JL1 minibody, immunonanoplex, leukemia therapy, siRNA

Article

Research Article

Mol. Cells 2010; 29(5): 457-462

Published online May 31, 2010 https://doi.org/10.1007/s10059-010-0056-5

Copyright © The Korean Society for Molecular and Cellular Biology.

Leukemia-Specific siRNA Delivery by Immunonanoplexes Consisting of Anti-JL1 Minibody Conjugated to Oligo-9 Arg-Peptides

Yeon Kyung Lee, Keun Sik Kim1, Jung Seok Kim, Jin Ee Baek, Sang Il Park, Hwa Yeon Jeong,Sang Soon Yoon2, Kyeong Cheon Jung2,3, Hyung Geun Song2,4, and Yong Serk Park*

Department of Biomedical Laboratory Science, Yonsei University, Wonju 220-710, Korea, 1Department of Biomedical Sciences, Youngdong University, Yeongdong 370-701, Korea, 2Department of Development and Manufacturing, Dinona Inc., Iksan 570-912, Korea, 3Department of Pathology, Seoul National University College of Medicine, Seoul 110-799, Korea, 4Department of Pathology, Chungbuk National University College of Medicine, Cheongju 361-763, Korea

Correspondence to:*Correspondence: parkys@yonsei.ac.kr

Received: September 25, 2010; Revised: December 29, 2010; Accepted: February 1, 2010

Abstract

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.

Keywords: 9-arginine peptide, anti-JL1 minibody, immunonanoplex, leukemia therapy, siRNA

Mol. Cells
Aug 31, 2022 Vol.45 No.8, pp. 513~602
COVER PICTURE
Cryo-EM structure of human porphyrin transporter ABCB6 (main figure) shows that binding of hemin (inset, magenta) in concert with two glutathione molecules (cyan) primes ABCB6 for high ATP turnover (Kim et al., pp. 575-587).

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