Abstract
High scalability of a novel bicyclic nucleoside building block, amido-bridged nucleic acid (AmNA), to diversify pharmacokinetic properties of therapeutic antisense oligonucleotides is described. N2'-functionalization of AmNA with a variety of hydrophobic groups is straightforward. Combinations of these modules display similar antisense knockdown effects and improve cellular uptake, relative to sequence-matched conventional 2',4'-bridged nucleic acid (2',4'-BNA) in vivo.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amines / chemistry*
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Animals
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Apolipoprotein C-III / genetics
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Apolipoprotein C-III / metabolism
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Drug Delivery Systems*
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Enzyme-Linked Immunosorbent Assay
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Hydrophobic and Hydrophilic Interactions*
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Liver / metabolism*
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Mice
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Oligonucleotides, Antisense / administration & dosage
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Oligonucleotides, Antisense / chemistry*
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Oligonucleotides, Antisense / pharmacokinetics*
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Organophosphorus Compounds / chemical synthesis
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Organophosphorus Compounds / chemistry
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
Substances
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Amines
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Apolipoprotein C-III
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Oligonucleotides, Antisense
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Organophosphorus Compounds
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RNA, Messenger
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phosphoramidite