We have developed the chemistry to conjugate a pyrroloindole tripeptide (CDPI3) analog of CC-1065 to the 5' or 3' ends of any oligodeoxyribonucleotide (ODN). The resultant conjugates hybridize sequence specifically to complementary DNA and RNA strands, yet do not interact with double-stranded DNA. The conjugated CDPI3 moiety can significantly stabilize short duplexes by binding to the minor groove. In light of these results, we propose to evaluate the potential of these conjugates as anti sense and antigene agents. The ability of ODN-CDPI3 conjugates to sequence specifically inhibit replication, transcription and translation will be investigated using simple in vitro model systems. Limited cell culture studies will be initiated to evaluate the potential of these modified ODNs for use as anti sense, anti-viral or anti-cancer agents.

Proposed Commercial Applications

Modified ODNs which form unusually stable hybrids usually elicit increased potency when used as antisense or antigene agents. Oligomers linked to a CC-1065-like minor groove binder form unusually stable hybrids. If these ODNs effectively block replication, transcription or translation in a sequence specific fashion, their commercial potential will be very high.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43GM052774-01A1
Application #
2191924
Study Section
Special Emphasis Panel (ZRG7-SSS-2 (02))
Project Start
1995-09-01
Project End
1996-02-28
Budget Start
1995-09-01
Budget End
1996-02-28
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Epoch Biosciences, Inc.
Department
Type
DUNS #
City
Bothell
State
WA
Country
United States
Zip Code
98021