Delivery of Phosphorodiamidate Morpholino Antisense Oligomers in Cancer Cells
Phosphorodiamidate morpholino oligomers (PMO), which have a neutral chemistry, are extensively being used as tools for selective inhibition of gene expression in cell culture models and are currently in human clinical trials. PMO oligomers possess a unique structure, in which the deoxyribose moiety of DNA is replaced with a six-membered morpholine ring and the charged phosphodiester internucleoside linkages are replaced with neutral phosphorodiamidate linkages. PMO internalization in uptake-permissive cells has been observed to be specific, saturable, and energy-dependent, suggesting a receptor-mediated uptake mechanism. Understanding PMO transport should facilitate the design of more effective synthetic antisense oligomers as therapeutic agents.
KeywordsApoptosis delivery fluorescence immunoblots morpholino oligonucleotides phosphorodiamidate PMO
I thank Katherine Aird and Rami Ghanayem for editorial and technical assistance and Dr. Patrick Iversen (Avi BioPharma Inc.). Some of the work presented here was supported by Department of Defense (DOD) grants DAMD17-01-1-0017 (GRD) and W81XWH-07-1-0392 (GRD).
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