Oligonucleotide analogs having cationic intersubunit linkages
First Claim
1. An oligomer comprising a sequence of morpholino subunits, each supporting a base-pairing moiety, such that said oligomer can bind in a sequence-specific manner to a target nucleic acid,wherein said subunits are joined by phosphorus-containing intersubunit linkages having the structure:
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Abstract
Morpholino oligomers containing both uncharged and cationic intersubunit linkages are provided. The oligomers are oligonucleotide analogs containing predetermined sequences of base-pairing moieties. The presence of the cationic intersubunit linkages in the oligomers, typically at a level of about 10-50% of total linkages, provides enhanced antisense activity, in various antisense applications, relative to the corresponding uncharged oligomers. Also provided are such oligomers conjugated to peptide transporter moieties, where the transporters are preferably composed of arginine subunits, or arginine dimers, alternating with neutral amino acid subunits.
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Citations
42 Claims
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1. An oligomer comprising a sequence of morpholino subunits, each supporting a base-pairing moiety, such that said oligomer can bind in a sequence-specific manner to a target nucleic acid,
wherein said subunits are joined by phosphorus-containing intersubunit linkages having the structure:
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31. A method of enhancing the antisense activity of an oligomeric nucleic acid analog having a sequence of morpholino subunits, each supporting a base-pairing moiety, wherein said subunits are connected by intersubunit linkages, the method comprising
modifying at least one intersubunit linkage to contain a pendant cationic group, wherein said pendant cationic group includes a nitrogen atom that can bear a positive charge at physiological pH.
Specification