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27 results on '"Hong, Cheol Am"'

5. Viral/Nonviral Chimeric Nanoparticles To Synergistically Suppress Leukemia Proliferation via Simultaneous Gene Transduction and Silencing

Author

Hong, Cheol Am, Cho, Soo Kyung, Edson, Julius A, Kim, Jane, Ingato, Dominique, Pham, Bryan, Chuang, Anthony, Fruman, David A, and Kwon, Young Jik

Subjects
Rare Diseases, Gene Therapy, Cancer, Hematology, Genetics, Antineoplastic Agents, Apoptosis, Benzamides, Cell Proliferation, Drug Resistance, Neoplasm, Fusion Proteins, bcr-abl, Gene Silencing, Genetic Therapy, Humans, K562 Cells, Leukemia, Nanoparticles, Piperazines, Protein Kinase Inhibitors, Pyrimidines, Transduction, Genetic, hybrid vector, core-shell nanoparticles, AAV transduction, RNA interference, BIM expression, MCL-1 silencing, synergistic leukemia gene therapy, core−shell nanoparticles, Nanoscience & Nanotechnology
Abstract

Single modal cancer therapy that targets one pathological pathway often turns out to be inefficient. For example, relapse of chronic myelogenous leukemia (CML) after inhibiting BCR-ABL fusion protein using tyrosine kinase inhibitors (TKI) (e.g., Imatinib) is of significant clinical concern. This study developed a dual modal gene therapy that simultaneously tackles two key BCR-ABL-linked pathways using viral/nonviral chimeric nanoparticles (ChNPs). Consisting of an adeno-associated virus (AAV) core and an acid-degradable polymeric shell, the ChNPs were designed to simultaneously induce pro-apoptotic BIM expression by the AAV core and silence pro-survival MCL-1 by the small interfering RNA (siRNA) encapsulated in the shell. The resulting BIM/MCL-1 ChNPs were able to efficiently suppress the proliferation of BCR-ABL+ K562 and FL5.12/p190 cells in vitro and in vivo via simultaneously expressing BIM and silencing MCL-1. Interestingly, the synergistic antileukemic effects generated by BIM/MCL-1 ChNPs were specific to BCR-ABL+ cells and independent of a proliferative cytokine, IL-3. The AAV core of ChNPs was efficiently shielded from inactivation by anti-AAV serum and avoided the generation of anti-AAV serum, without acute toxicity. This study demonstrates the development of a synergistically efficient, specific, and safe therapy for leukemia using gene carriers that simultaneously manipulate multiple and interlinked pathological pathways.

Published
2016

26. Viral/Nonviral Chimeric Nanoparticles To Synergistically Suppress Leukemia Proliferation viaSimultaneous Gene Transduction and Silencing

Author

Hong, Cheol Am, Cho, Soo Kyung, Edson, Julius A., Kim, Jane, Ingato, Dominique, Pham, Bryan, Chuang, Anthony, Fruman, David A., and Kwon, Young Jik

Abstract

Single modal cancer therapy that targets one pathological pathway often turns out to be inefficient. For example, relapse of chronic myelogenous leukemia (CML) after inhibiting BCR-ABL fusion protein using tyrosine kinase inhibitors (TKI) (e.g., Imatinib) is of significant clinical concern. This study developed a dual modal gene therapy that simultaneously tackles two key BCR-ABL-linked pathways using viral/nonviral chimeric nanoparticles (ChNPs). Consisting of an adeno-associated virus (AAV) core and an acid-degradable polymeric shell, the ChNPs were designed to simultaneously induce pro-apoptotic BIM expression by the AAV core and silence pro-survival MCL-1 by the small interfering RNA (siRNA) encapsulated in the shell. The resulting BIM/MCL-1 ChNPs were able to efficiently suppress the proliferation of BCR-ABL+ K562 and FL5.12/p190 cells in vitroand in vivoviasimultaneously expressing BIM and silencing MCL-1. Interestingly, the synergistic antileukemic effects generated by BIM/MCL-1 ChNPs were specific to BCR-ABL+ cells and independent of a proliferative cytokine, IL-3. The AAV core of ChNPs was efficiently shielded from inactivation by anti-AAV serum and avoided the generation of anti-AAV serum, without acute toxicity. This study demonstrates the development of a synergistically efficient, specific, and safe therapy for leukemia using gene carriers that simultaneously manipulate multiple and interlinked pathological pathways.

Published
2016
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27. Reductively Dissociable siRNA-Polymer Hybrid Nanogels for Efficient Targeted Gene Silencing.

Author

Hong, Cheol Am, Kim, Jee Seon, Lee, Soo Hyeon, Kong, Won Ho, Park, Tae Gwan, Mok, Hyejung, and Nam, Yoon Sung

Abstract

A highly efficient approach for target-specific gene silencing based on a reductively dissociable nanogel incorporating small interfering RNA (siRNA) crosslinked with linear polyethylenimine (LPEI) via disulfide bonds is presented. Thiol-terminated siRNA at both 3′-ends is electrostatically complexed with thiol-grafted LPEI. The prepared siRNA/LPEI complex contains inter- and intramolecular linkages, generating a mutually crosslinked siRNA/LPEI nanogel (MCN) that exhibits excellent structural stability against the addition of heparin but is readily disintegrated to biologically active, monomeric siRNA upon exposure to reductive conditions. Accordingly, the highly condensed, stable MCN shows greatly enhanced cellular uptake and gene silencing efficiency compared to the siRNA/LPEI complexes without crosslinks or with only LPEI-mediated crosslinks. [ABSTRACT FROM AUTHOR]

Published
2013
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