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WO1997043404A3 - Ribozyme variants with improved catalytic activity under low magnesium conditions - Google Patents

Ribozyme variants with improved catalytic activity under low magnesium conditions Download PDF

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Publication number
WO1997043404A3
WO1997043404A3 PCT/US1997/008101 US9708101W WO9743404A3 WO 1997043404 A3 WO1997043404 A3 WO 1997043404A3 US 9708101 W US9708101 W US 9708101W WO 9743404 A3 WO9743404 A3 WO 9743404A3
Authority
WO
WIPO (PCT)
Prior art keywords
variants
catalytic activity
activity under
under low
improved catalytic
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.)
Ceased
Application number
PCT/US1997/008101
Other languages
French (fr)
Other versions
WO1997043404A2 (en
Inventor
Martin Zillman
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.)
Aceragen Inc
Original Assignee
Hybridon Inc
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
Application filed by Hybridon Inc filed Critical Hybridon Inc
Priority to AU30056/97A priority Critical patent/AU3005697A/en
Publication of WO1997043404A2 publication Critical patent/WO1997043404A2/en
Publication of WO1997043404A3 publication Critical patent/WO1997043404A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/11—Antisense
    • C12N2310/111—Antisense spanning the whole gene, or a large part of it
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/12—Type of nucleic acid catalytic nucleic acids, e.g. ribozymes
    • C12N2310/121—Hammerhead
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/321—2'-O-R Modification

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Catalysts (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Disclosed are ribozyme variants and structures making up the catalytic portions of ribozyme variants having enhanced catalytic activity under no turnover conditions in the presence of less than or equal to 10 millimolar concentrations of magnesium. Also disclosed are plasmids encoding such variants, and methods of controlling the expression of a target RNA molecule and of site-specifically cleaving a single-stranded, RNA-containing substrate molecule using such variants.
PCT/US1997/008101 1996-05-13 1997-05-13 Ribozyme variants with improved catalytic activity under low magnesium conditions Ceased WO1997043404A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU30056/97A AU3005697A (en) 1996-05-13 1997-05-13 Ribozyme variants with improved catalytic activity under low magnesium conditions

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US64757796A 1996-05-13 1996-05-13
US08/647,577 1996-05-13
US80054997A 1997-02-18 1997-02-18
US08/800,549 1997-02-18

Publications (2)

Publication Number Publication Date
WO1997043404A2 WO1997043404A2 (en) 1997-11-20
WO1997043404A3 true WO1997043404A3 (en) 1997-12-24

Family

ID=27095188

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1997/008101 Ceased WO1997043404A2 (en) 1996-05-13 1997-05-13 Ribozyme variants with improved catalytic activity under low magnesium conditions

Country Status (2)

Country Link
AU (1) AU3005697A (en)
WO (1) WO1997043404A2 (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AR020329A1 (en) * 1998-07-09 2002-05-08 Boehringer Ingelheim Pharma A SUBSTANCE, IN PARTICULAR A RIBOZIMA, IS ABLE TO INHIBIT THE PRESENILINE EXPRESSION 2, A RECOMBINATING MOLECULA OF DNA THAT CODIFY SUCH RIBOZIMA, A RECOMBINATING UNVECTOR THAT UNDERSTANDS THE CORRECTING CELL TO A RIBO BELLING ONE.
US9476089B2 (en) 2012-10-18 2016-10-25 President And Fellows Of Harvard College Methods of making oligonucleotide probes

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996000232A1 (en) * 1994-06-24 1996-01-04 Gene Shears Pty. Ltd. RIBOZYMES WITH OPTIMIZED HYBRIDIZING ARMS, STEMS, AND LOOPS, tRNA EMBEDDED RIBOZYMES AND COMPOSITIONS THEREOF

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996000232A1 (en) * 1994-06-24 1996-01-04 Gene Shears Pty. Ltd. RIBOZYMES WITH OPTIMIZED HYBRIDIZING ARMS, STEMS, AND LOOPS, tRNA EMBEDDED RIBOZYMES AND COMPOSITIONS THEREOF

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
AMONTOV, S. & TAIRA, K.: "Hammerhead minizymes with high cleavage activity: a dimeric structure as the active conformation of minizymes", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY., vol. 118, 21 February 1996 (1996-02-21), DC US, pages 1624 - 1628, XP002045193 *
BEIGELMAN L ET AL: "CHEMICAL MODIFICATION OF HAMMERHEAD RIBOZYMES CATALYTIC ACTIVITY AND NUCLEASE RESISTANCE", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 270, no. 43, 27 October 1995 (1995-10-27), pages 25702 - 25708, XP000601905 *
BENSELER, F. ET AL.: "Hammerhead-like molecules containing non-nucleoside linkers are active RNA catalysts", J. AM. CHEM. SOC. (1993), 115(18), 8483-4, XP000644539 *
BIRIKH, K. ET AL.: "The structure, function and application of the hammerhead ribozyme", EUROPEAN JOURNAL OF BIOCHEMISTRY, vol. 245, April 1997 (1997-04-01), pages 1 - 16, XP002045195 *
CRISELL P ET AL: "Inhibition of HIV-1 replication by ribozymes that show poor activity in vitro.", NUCLEIC ACIDS RESEARCH, (1993 NOV 11) 21 (22) 5251-5., XP002045190 *
GOODCHILD J ET AL: "RIBOZYMES THAT CLEAVE AN RNA SEQUENCE FROM HUMAN IMMUNODEFICIENCY VIRUS: THE EFFECT OF FLANKING SEQUENCE ON RATE", ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, vol. 284, no. 2, 1 February 1991 (1991-02-01), pages 386 - 391, XP000609191 *
ISHIZAKA, M. ET AL.: "Isolation of active ribozymes from an RNA pool of random sequences using an anchored substrate RNA", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS., vol. 214, 14 September 1995 (1995-09-14), ORLANDO, FL US, pages 403 - 409, XP002045192 *
TUSCHL T ET AL: "Hammerhead ribozymes: importance of stem -loop II for activity.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, (1993 AUG 1) 90 (15) 6991-4., XP002045191 *
ZILLMANN M ET AL: "In vitro optimization of truncated stem -loop II variants of the hammerhead ribozyme for cleavage in low concentrations of magnesium under non - turnover conditions.", RNA, (1997 JUL) 3 (7) 734-47., XP002045194 *

Also Published As

Publication number Publication date
AU3005697A (en) 1997-12-05
WO1997043404A2 (en) 1997-11-20

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