title: Leukemia-specific siRNA delivery by immunonanoplexes consisting of anti-JL1 minibody conjugated to oligo-9 Arg-peptides.
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 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.
authors.affiliation: Department of Biomedical Laboratory Science, Yonsei University, Wonju, 220-710, Korea.
authors.forename: Yeon Kyung
authors.initials: YK
authors.lastname: Lee
authors.forename: Keun Sik
authors.initials: KS
authors.lastname: Kim
authors.forename: Jung Seok
authors.initials: JS
authors.lastname: Kim
authors.forename: Jin Ee
authors.initials: JE
authors.lastname: Baek
authors.forename: Sang Il
authors.initials: SI
authors.lastname: Park
authors.forename: Hwa Yeon
authors.initials: HY
authors.lastname: Jeong
authors.forename: Sang Soon
authors.initials: SS
authors.lastname: Yoon
authors.forename: Kyeong Cheon
authors.initials: KC
authors.lastname: Jung
authors.forename: Hyung Geun
authors.initials: HG
authors.lastname: Song
authors.forename: Yong Serk
authors.initials: YS
authors.lastname: Park
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D051379:Mice; D016513:Mice, SCID; D018613:Microscopy, Confocal; D009368:Neoplasm Transplantation; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015202:Protein Engineering; D034741:RNA, Small Interfering / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; C114952:JL1 antigen; D010446:Peptide Fragments; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins