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Liposomal delivery of oligodeoxynucleotides
A Tari1, M Khodadadian, D Ellerson
1Department of Bioimmunotherapy, The University of Texas, M. D. Anderson Cancer Center, Houston 770303, USA.
Leukemia & Lymphoma
|March 1, 1996
Summary
Liposomes effectively deliver antisense oligonucleotides (oligos) to chronic myelogenous leukemia cells, inhibiting cancer cell proliferation. This liposomal delivery method shows promise for overcoming challenges in developing antisense therapies.
Area of Science:
- Oncology
- Molecular Biology
- Drug Delivery
Background:
- Antisense oligodeoxynucleotides (oligos) targeting BCR-ABL can inhibit chronic myelogenous leukemia (CML) cell proliferation.
- Clinical development of antisense oligos is hindered by limitations such as poor cellular uptake and stability.
Purpose of the Study:
- To evaluate the efficacy of liposome-entrapped antisense oligos for treating CML.
- To investigate the intracellular localization and toxicity of liposomal oligos in leukemia models.
Main Methods:
- Liposome-entrapment of methylphosphonate, phosphodiester, and phosphorothioate antisense oligos specific for BCR-ABL.
- In vitro studies using CML cell lines.
- Fluorescent microscopy for intracellular liposome localization.
- Toxicity assays on normal peripheral blood mononuclear cells and bone marrow progenitors.
Main Results:
- Liposome-entrapped oligos selectively inhibited CML cell proliferation.
- Liposomes were readily taken up by leukemic cells and localized in the cytoplasm.
- Liposomal oligos demonstrated no toxicity to normal hematopoietic cells.
Conclusions:
- Liposomal delivery of antisense oligos is effective in inhibiting CML cell proliferation.
- Liposomal delivery enhances intracellular access of oligos to target cells.
- This approach may overcome major limitations for the clinical development of antisense oligos.