Title:
NON-INVASIVE METHOD FOR DETECTING TARGET RNA
Document Type and Number:
WIPO Patent Application WO2002048405
Kind Code:
A3
Abstract:
A method of detecting in a subject, the occurrence of a base-specific intracellular binding event involving a single-stranded target RNA, is disclosed. The method includes administering to the subject an oligomeric antisense compound having (i) from 8 to 40 bases, including a targeting base sequence that is complementary to a portion of the target RNA, (ii) a Tm, with respect to binding to a complementary RNA sequence, of greater than about 50 DEG C, and (iii) an ability to be actively taken up mammalian cells, and (iv) conferring resistance of complementary RNA hybridized with the agent to RnaseH. Where the compound is administered in uncomplexed form, it preferably has a substantially backbone. At a selected time after said administering the agent, a sample of a body fluid is obtained from the subject, and the presence in the sample of a nuclease-resistant heteroduplex composed of the antisense oligomer and the complementary portion of the target RNA is detected. The method is useful, for example, for detecting levels of gene expression, biochemical or physiological states that are characterized by expression of certain genes, genetic mutation, and the presence and identity of infective viral or bacterial agents. Also disclosed are arrays, kits and antibodies employed in carrying out the method.
Inventors:
IVERSEN PATRICK L
Application Number:
PCT/US2001/048694
Publication Date:
August 21, 2003
Filing Date:
December 13, 2001
Export Citation:
Assignee:
AVI BIOPHARMA INC (US)
International Classes:
G01N33/53; A61K48/00; C07K16/08; C07K16/12; C07K16/44; C12N15/113; C12P21/08; C12Q1/68; G01N33/566; G01N33/569; A61K38/00; (IPC1-7): C12Q1/68
Domestic Patent References:
| WO2000044897A1 | 2000-08-03 | |||
| WO1991009033A1 | 1991-06-27 |
Other References:
BONHAM MICHELE A ET AL: "An assessment of the antisense properties of RNase H-competent and steric-blocking oligomers.", NUCLEIC ACIDS RESEARCH, vol. 23, no. 7, 1995, pages 1197 - 1203, XP001152649, ISSN: 0305-1048
MIR KALIM U ET AL: "Determining the influence of structure on hybridization using oligonucleotide arrays.", NATURE BIOTECHNOLOGY, vol. 17, no. 8, August 1999 (1999-08-01), pages 788 - 792, XP001152622, ISSN: 1087-0156
MONIA B P ET AL: "EVALUATION OF 2'-MODIFIED OLIGONUCLEOTIDES CONTAINING 2'-DEOXY GAPS AS ANTISENSE INHIBITORS OF GENE EXPRESSION", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY OF BIOLOGICAL CHEMISTS, BALTIMORE, MD, US, vol. 268, no. 19, 5 July 1993 (1993-07-05), pages 14514 - 14522, XP000576145, ISSN: 0021-9258
LEE REACHING ET AL: "Polyamide nucleic acid targeted to the primer binding site of the HIV-1 RNA genome blocks in vitro HIV-1 reverse transcription.", BIOCHEMISTRY, vol. 37, no. 3, 20 January 1998 (1998-01-20), pages 900 - 910, XP002242997, ISSN: 0006-2960
FARIA M ET AL: "PHOSPHORAMIDATE OLIGONUCLEOTIDES AS POTENT ANTISENSE MOLECULES IN CELLS AND IN VIVO", NATURE BIOTECHNOLOGY, NATURE PUBLISHING, US, vol. 19, no. 1, January 2001 (2001-01-01), pages 40 - 44, XP001075021, ISSN: 1087-0156
MIR KALIM U ET AL: "Determining the influence of structure on hybridization using oligonucleotide arrays.", NATURE BIOTECHNOLOGY, vol. 17, no. 8, August 1999 (1999-08-01), pages 788 - 792, XP001152622, ISSN: 1087-0156
MONIA B P ET AL: "EVALUATION OF 2'-MODIFIED OLIGONUCLEOTIDES CONTAINING 2'-DEOXY GAPS AS ANTISENSE INHIBITORS OF GENE EXPRESSION", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY OF BIOLOGICAL CHEMISTS, BALTIMORE, MD, US, vol. 268, no. 19, 5 July 1993 (1993-07-05), pages 14514 - 14522, XP000576145, ISSN: 0021-9258
LEE REACHING ET AL: "Polyamide nucleic acid targeted to the primer binding site of the HIV-1 RNA genome blocks in vitro HIV-1 reverse transcription.", BIOCHEMISTRY, vol. 37, no. 3, 20 January 1998 (1998-01-20), pages 900 - 910, XP002242997, ISSN: 0006-2960
FARIA M ET AL: "PHOSPHORAMIDATE OLIGONUCLEOTIDES AS POTENT ANTISENSE MOLECULES IN CELLS AND IN VIVO", NATURE BIOTECHNOLOGY, NATURE PUBLISHING, US, vol. 19, no. 1, January 2001 (2001-01-01), pages 40 - 44, XP001075021, ISSN: 1087-0156
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