Hybrid oligonucleotide phosphorothioates

• US 5,652,355 A
• Filed: 07/23/1992
• Issued: 07/29/1997
• Est. Priority Date: 07/23/1992
• Status: Expired due to Term

• Current Assignee: University Of Massachusetts
• Original Assignee: Worcester Foundation For Experimental Biology
• Inventors: Agrawal, Sudhir, Metelev, Valeri
• Primary Examiner(s): RORIES, CHARLES
• Application Number:
  US07/918,239
• Time in Patent Office: 1,832 Days
• Field of Search: 514/44, 536/24.5, 536/23.1, 536/24.3, 536/24.31, 536/24.32, 935/6, 935/9, 935/11, 935/34, 435/6
• US Class Current: 536/24.5
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 33/02 Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 15/1132 against retroviridae, e.g. HIV
• CPC Class Codes: C12N 2310/313 Phosphorodithioates
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/341 Gapmers, i.e. of the type ===---===
• CPC Class Codes: C12N 2310/346 having a combination of backbone and sugar modifications
• CPC Class Codes: C12N 2310/3521 Methyl

Abstract

The invention provides hybrid oligonucleotides having phosphorothioate or phosphorodithioate internucleotide linkages, and both deoxyribonucleosides and ribonueleosides or 2'"'"'-substituted ribonucleosides. Such hybrid oligonucleotides have superior properties of duplex formation with RNA, nuclease resistance, and RNase H activation.

Claims

1. A hybrid oligonucleotide that is complementary to a target RNA, the hybrid oligonucleotide consisting of phosphorothioate nucleotides and comprising a segment of at least two contiguous 2'"'"'-O-methyl-substituted ribonucleotides as the terminal two nucleotides at each end of the oligonucleotide, and further comprising a segment of at least three contiguous deoxyribonucleotides.

2. A hybrid oligonucleotide according to claim 1, wherein the deoxyribonucleotide is present in a segment of at least four contiguous deoxyribonucleotides.

3. An oligonucleotide according to claim 1 comprising from about 6 to about 50 nucleotides.

4. An oligonucleotide according to claim 2 comprising from about 6 to about 50 nucleotides.

5. An oligonucleotide according to claim 1 wherein the target RNA is a RNA from a virus.

6. An oligonucleotide according to claim 2 wherein the target RNA is a RNA from a virus.

7. An oligonucleotide according to claim 3 wherein the target RNA is a RNA from a virus.

8. An oligonucleotide according to claim 4 wherein the target RNA is a RNA from a virus.

9. An oligonucleotide according to claim 1 wherein the target RNA is a RNA from HIV.

10. An oligonucleotide according to claim 2 wherein the target RNA is a RNA from HIV.

11. An oligonucleotide according to claim 3 wherein the target RNA is a RNA from HIV.

12. An oligonucleotide according to claim 4 wherein the target RNA is a RNA from HIV.