Leukemia-specific siRNA delivery by immunonanoplexes consisting of anti-JL1 minibody conjugated to oligo-9 Arg-peptides |
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Authors: | Yeon Kyung Lee Keun Sik Kim Jung Seok Kim Jin Ee Baek Sang Il Park Hwa Yeon Jeong Sang Soon Yoon Kyeong Cheon Jung Hyung Geun Song Yong Serk Park |
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Institution: | (1) Optimum Therapeutics LLC, The Ohio State University Science Tech Village, Columbus, Ohio 43212, USA |
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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. |
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