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Abstract:
We are developing bifunctional agents to reduce HER-2/neu overexpression in breast cancer based on a design coupling an "active" site antisense DNA to a "binding" element. The active site is a DNA hexamer which targets a loop region in the 5'-untranslated region (UTR) of HER- 2/neu mRNA. We produced chimeric anti sense agents consisting of this active site linked to a binding 2'-O-methy RNA hexamer targeted to another loop region and optimized the linkage between those sites for RNaseH digestion of the target RNA. Cyclic peptide binding moieties have also been optimized. Experiments are in progress to test the efficacy of the new agents in reducing HER-2/neu expression in vitro and in cultured cells.
| Limitations: |
 APPROVED FOR PUBLIC RELEASE |
| Description: |
Annual rept. 1 Jul 1999-30 Jun 2000 |
| Pages: |
27 |
| Report Date: |
JUL 2000 |
| Contract Number: |
DAMD17-97-1-7288 |
| Report Number: |
A327093 |
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