CA2259144A1 - Inhibition of chronic myelogenous leukemic cell growth by liposomal-antisense oligodeoxy-nucleotides targeting to grb2 or crk1 - Google Patents

Inhibition of chronic myelogenous leukemic cell growth by liposomal-antisense oligodeoxy-nucleotides targeting to grb2 or crk1

Info

Publication number
CA2259144A1
CA2259144A1 CA 2259144 CA2259144A CA2259144A1 CA 2259144 A1 CA2259144 A1 CA 2259144A1 CA 2259144 CA2259144 CA 2259144 CA 2259144 A CA2259144 A CA 2259144A CA 2259144 A1 CA2259144 A1 CA 2259144A1
Authority
CA
Grant status
Application
Patent type
Prior art keywords
polynucleotide
composition
hybridizes
method
translation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA 2259144
Other languages
French (fr)
Other versions
CA2259144C (en )
Inventor
Gabriel Lopez-Berestein
Ana M. Tari
Ralph B. Arlinghaus
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Texas System
Original Assignee
Board Of Regents, The University Of Texas System
Gabriel Lopez-Berestein
Ana M. Tari
Ralph B. Arlinghaus
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date

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Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113Non-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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K48/00Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/10Type of nucleic acid
    • C12N2310/11Antisense
    • C12N2310/111Antisense spanning the whole gene, or a large part of it
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/31Chemical structure of the backbone
    • C12N2310/311Phosphotriesters
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2799/00Uses of viruses
    • C12N2799/02Uses of viruses as vector
    • C12N2799/021Uses of viruses as vector for the expression of a heterologous nucleic acid

Abstract

The present invention provides novel compositions and methods for use in the treatment of cancer, specifically, in the treatment of chronic myelogenous leukemia (CML). The compositions contain antisense oligonucleotides that hybridize to Grb2 and Crk1 nucleic acids, the gene products of which are known to interact with the tumorigenic protein bcr-abl. Used alone, in conjunction with each other, and even in conjunction with antisense oligonucleotides directed to bcr-abl nucleic acids, these compositions inhibit the proliferation of CML cancer cells.

Claims (26)

1. A composition comprising a polynucleotide that hybridizes to the translation initiation site of a Grb2-encoding polynucleotide.
2. A composition comprising a polynucleotide that hybridizes to the translation initiation site of a Crkl-encoding polynucleotide.
3. The composition of claim 1, wherein said polynucleotide is an oligonucleotide having a length of 8-50 bases.
4. The composition of claim 2, wherein said polynucleotide is an oligonucleotide having a length of 8-50 bases.
5. The composition of claim 1, wherein the polynucleotide is an oligonucleotide having the sequence ATATTTGGCGATGGCTTC (SEQ ID NO: 5).
6. The composition of claim 2, wherein the polynucleotide is an oligonucleotide having the sequence GTCGAACCGGCGGAGGA (SEQ ID NO: 6).
7. The composition of claim 1, further comprising a liposome in which said polynucleotide is encapsulated.
8. The composition of claim 2, further comprising a liposome in which said polynucleotide is encapsulated.
9. The composition of claim 7, wherein said liposome comprises the lipid dioleoylphosphatidylcholine.
10. The composition of claim 8, wherein said liposome comprises the lipid dioleoylphosphatidylcholine.
11. A composition comprising (i) a polynucleotide that hybridizes to a Grb2-encoding polynucleotide or (ii) a polynucleotide that hybridizes to a Crk1-encoding polynucleotide.
12. The composition of claim 11, further comprising a polynucleotide that hybridizes to a bcr-abl-encoding polynucleotide.
13. A composition comprising an expression construct that encodes a first polynucleotide that hybridizes to the translation start site of a Grb2-encoding polynucleotide, wherein said first polynucleotide is under the control of a promoter that is active in eukaryotic cells.
14. A composition comprising an expression construct that encodes a first polynucleotide that hybridizes to the translation start site of a Crk1-encoding polynucleotide, wherein said first polynucleotide is under the control of a promoter that is active in eukaryotic cells.
15. A method for inhibiting proliferation of a cancer cell comprising contacting said cancer cell with a composition comprising at least (i) a polynucleotide that hybridizes to the translation start site of a Grb2 nucleic acid or (ii) a polynucleotide that hybridizes to the translation start site of a Crk1 nucleic acid.
16. The method of claim 15, wherein said polynucleotides are oligonucleotides having a length of 8-50 bases.
17. The method of claim 16, wherein said composition further comprises a polynucleotide that hybridizes to a bcr-abl nucleic acid.
18. The method of claim 17 wherein said composition comprises both (i) a polynucleotide that hybridizes to the translation start site of a Grb2 nucleic acid or (ii) a polynucleotide that hybridizes to the translation start site of a Crk1 nucleic acid.
19. The method of claim 16, wherein said cancer cell is a leukemia cell.
20. The method of claim 19, wherein said cancer cell is a chronic myelogenous leukemia cell.
21. The method of claim 16, wherein said composition further comprises a liposome in which said polynucleotide is encapsulated.
22. The method of claim 16, wherein said contacting takes place in a patient.
23. The method of claim 22, wherein said patient is a human.
24. The method of claim 22, wherein said composition is delivered to said human in a volume of 0.50-10.0 ml per dose.
25. The method of claim 22, wherein said composition is delivered to said human in an amount of 5-30 mg polynucleotide per m2.
26. The method of claim 25, wherein said composition is administered three times per week for eight weeks.
CA 2259144 1996-07-08 1997-07-08 Inhibition of chronic myelogenous leukemic cell growth by liposomal-antisense oligodeoxy-nucleotides targeting to grb2 or crk1 Expired - Fee Related CA2259144C (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
US08/679,437 1996-07-08
US08679437 US7309692B1 (en) 1996-07-08 1996-07-08 Inhibition of chronic myelogenous leukemic cell growth by liposomal-antisense oligodeoxy-nucleotides targeting to GRB2 or CRK1
PCT/US1997/010101 WO1998001547A1 (en) 1996-07-08 1997-07-08 INHIBITION OF CHRONIC MYELOGENOUS LEUKEMIC CELL GROWTH BY LIPOSOMAL-ANTISENSE OLIGODEOXY-NUCLEOTIDES TARGETING TO Grb2 OR Crk1

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CA 2741501 CA2741501A1 (en) 1996-07-08 1997-07-08 Inhibition of chronic myelogenous leukemic cell growth by liposomal-antisense oligodeoxy-nucleotides targeting to grb2 or crk1

Publications (2)

Publication Number Publication Date
CA2259144A1 true true CA2259144A1 (en) 1998-01-15
CA2259144C CA2259144C (en) 2011-09-20

Family

ID=24726909

Family Applications (2)

Application Number Title Priority Date Filing Date
CA 2259144 Expired - Fee Related CA2259144C (en) 1996-07-08 1997-07-08 Inhibition of chronic myelogenous leukemic cell growth by liposomal-antisense oligodeoxy-nucleotides targeting to grb2 or crk1
CA 2741501 Abandoned CA2741501A1 (en) 1996-07-08 1997-07-08 Inhibition of chronic myelogenous leukemic cell growth by liposomal-antisense oligodeoxy-nucleotides targeting to grb2 or crk1

Family Applications After (1)

Application Number Title Priority Date Filing Date
CA 2741501 Abandoned CA2741501A1 (en) 1996-07-08 1997-07-08 Inhibition of chronic myelogenous leukemic cell growth by liposomal-antisense oligodeoxy-nucleotides targeting to grb2 or crk1

Country Status (7)

Country Link
US (3) US7309692B1 (en)
EP (2) EP1234876B1 (en)
JP (1) JP2000514438A (en)
CA (2) CA2259144C (en)
DE (4) DE69738459T2 (en)
ES (2) ES2299536T3 (en)
WO (1) WO1998001547A1 (en)

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JP2008536874A (en) 2005-04-15 2008-09-11 ボード オブ リージェンツ ザ ユニバーシティー オブ テキサス システム Delivery of siRNA by the neutral lipid composition
WO2009149418A3 (en) * 2008-06-06 2010-03-25 Asuragen, Inc. Compositions for the in vivo delivery of rnai agents
JP2011525491A (en) * 2008-06-20 2011-09-22 ザ ボード オブ リージェンツ オブ ザ ユニバーシティー オブ テキサス システム Crkl targeting peptide
CA3001005A1 (en) 2015-10-14 2017-04-20 Bio-Path Holding, Inc. P-ethoxy nucleic acids for liposomal formulation
WO2018053232A1 (en) * 2016-09-16 2018-03-22 Bio-Path Holdings, Inc. Combination therapy with liposomal antisense oligonucleotides

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Also Published As

Publication number Publication date Type
EP0912729A1 (en) 1999-05-06 application
DE69736290T2 (en) 2007-07-05 grant
DE69738459D1 (en) 2008-02-21 grant
US7923548B2 (en) 2011-04-12 grant
EP0912729B1 (en) 2006-07-05 grant
US7220853B2 (en) 2007-05-22 grant
ES2299536T3 (en) 2008-06-01 grant
ES2268731T3 (en) 2007-03-16 grant
DE69736290D1 (en) 2006-08-17 grant
EP1234876A1 (en) 2002-08-28 application
US20030153526A1 (en) 2003-08-14 application
CA2741501A1 (en) 1998-01-15 application
DE69738459T2 (en) 2008-12-24 grant
US20070238686A1 (en) 2007-10-11 application
EP1234876B1 (en) 2008-01-09 grant
JP2000514438A (en) 2000-10-31 application
US7309692B1 (en) 2007-12-18 grant
WO1998001547A1 (en) 1998-01-15 application
CA2259144C (en) 2011-09-20 grant

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