Isis Pharmaceuticals, Inc.

Sterling Winthrop Inc.

Philip D Cook

Yogesh S Sanghvi

Charles John Guinosso

Andrew Mamoru Kawasaki

Daniel J Delecki

Charles Guinosso

Compositions and methods are provided for the treatment and diagnosis of diseases amenable to modulation of the production of selected proteins. In accordance with preferred embodiments, oligonucleotides and oligonucleotide analogs are provided which are specifically hybridizable with a selected sequence of RNA or DNA wherein at least one of the 2&prime;-deoxyfuranosyl moieties of the nucleoside unit is modified. Treatment of HIV, herpes virus, papillomavirus and other infections is provided.

Sugar modified oligonucleotides that detect and modulate gene expression

Nuclease resistant, pyrimidine modified oligonucleotides that detect and

Compounds of formula I; ##STR1## wherein R.sup.1 is hydrogen, or a blocking group that is compatible with oligonucleotide synthesis;

Acyclic nucleoside analogs and oligonucleotide sequences containing them

Therapeutic oligonucleotide analogs which have improved nuclease resistance and improved cellular uptake are provided. Replacement of the normal phosphorodiester inter-sugar linkages found in wild type oligomers with four atom linking groups forms unique di- and poly- nucleosides and nucleotides useful in regulating RNA expression and in therapeutics. Methods of synthesis and use are also disclosed.

Backbone modified oligonucleotide analogs

Novel oligonucleotide analogs are provided having improved cellular uptake, improved resistance to nucleases, and good hybridization to target RNA. Such analogs are provided having substantially non-chiral, non-ionic linking functionalities between the sugars and sugar analogs thereof. In accordance with preferred embodiments, the 4' position of a sugar or sugar analog at one nucleoside is linked to the 3' position of a second sugar or sugar analog of a second nucleoside by a linking function that comprises a two- or three- carbon backbone chain. In accordance with preferred embodiments, the linking functions comprise the formula)--R.sub.1 --O where R.sub.1 comprises a two or three carbon backbone. Such linking functions also, preferably comprise ether functionalities to effect such linkage. Processes for the automated synthesis of oligonucleotide analogs are also provided.

4'-desmethyl nucleoside analog compounds

Oligonucleotide analogs are provided having improved cellular uptake and improved nuclease resistance. Modification of oligonucleotides through the attachment of nitrogenous moieties, especially polyamines, hydrazines and the like to nucleosidic portions of the analogs is disclosed. Oligonucleotides targeted at the tat region of HIV comprise certain preferred embodiments.

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Carlsbad, CA, United States of America

Philip D Cook