Isis Pharmaceuticals, Inc.

Gilead Sciences, Inc.

Rick Wagner

Brian C Froehler

Robert J Jones

Arnold J Gutierrez

Jeff Pudlo

Mark D Matteucci

Kuei-Ying Lin

Norbert W Bischofberger

Chris A Buhr

Mark Mattencci

Ken Kent

Novel oligomers are disclosed which have enhanced ability with respect to forming duplexes or triplexes compared with oligomers containing only conventional bases. The oligomers contain the bases 5-(1-propynyl)uracil, 5-(1-propynyl)cytosine or related analogs. The oligomers of the invention are capable of (i) forming triplexes with various target sequences such as virus or oncogene sequences by coupling into the major groove of a target DNA duplex at physiological pH or (ii) forming duplexes by binding to single-stranded DNA or to RNA encoded by target genes. The oligomers of the invention can be incorporated into pharmaceutically acceptable carriers and can be constructed to have any desired sequence, provided the sequence normally includes one or more bases that is replaced with the analogs of the invention. Compositions of the invention can be used as pharmaceutical agents to treat various diseases such as those caused by viruses and can be used for diagnostic purposes in order to detect viruses or disease conditions.

Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines

Novel oligomers are disclosed which have enhanced ability with respect to forming duplexes or triplexes compared with oligomers containing only conventional bases. The oligomers contain the bases 5-(1-propynyl)uracil, 5-(1-propynyl)cytosine or related analogs. The oligomers of the invention are capable of (i) forming triplexes with various target sequences such as virus or oncogene sequences by coupling into the major groove of a target DNA duplex at physiological pH or (ii) forming duplexes by binding to single-stranded DNA or to RNA encoded by target genes. The oligomers of the invention can be incorporated into pharmaceutically acceptable carriers and can be constructed to have any desired sequence, provided the sequence normally includes one or more bases that is replaced with the analogs of the invention. compositions of the invention can be used as pharmaceutical agents to treat various diseases such as those caused by viruses and can be used for diagnostic purposes in order to detect viruses or disease conditions.

Methods of using oligomers containing modified pyrimidines

Oligonucleotides that are capable of passive diffusion across cell membranes are disclosed. These oligonucleotides contain at least two nucleotide residues and show a log distribution coefficient in octanol:water of about 0.0-2.5 and a solubility in water of at least 0.001 .mu.g/mL. In preferred embodiments, either at least 80% of the internucleotide linkages are non-ionic, or at least 80% of the bases contain lipophilic hydrocarbyl substitutions, or a combination of these sums to 80%. These oligonucleotides may be conjugated to label and used to visualize cells.

Oligonucleotides and their analogs capable of passive cell membrane

Novel oligomers are disclosed which have enhanced ability with respect to forming duplexes or triplexes compared with oligomers containing only conventional bases. The oligomers contain the bases 5-(1-propynyl)uracil, 5-(1-propynyl)cytosine or related analogs. The oligomers of the invention are capable of (i) forming triplexes with various target sequences such as virus or oncogene sequences by coupling into the major groove of a target DNA duplex at physiological pH or (ii) forming duplexes by binding to single-stranded DNA or to RNA encoded by target genes. The oligomers of the invention can be constructed to have any desired sequence, provided the sequence normally includes one or more bases that is replaced with the analogs of the invention. Compositions of the invention can be used used for diagnostic purposes in order to detect viruses or disease conditions.

Enhanced triple-helix and double-helix formation with oligomers

Oligonucleotide analogs capable of passive cell membrane permeation

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Belmont, CA, United States of America

Rick Wagner