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Abstract
Grant Number: 2R42GM057712-02A1 PI Name: STANOJEVIC, DUSAN PI Email: ds@crosslinkgenetics.com PI Title: Project Title: Method for Discovering Novel Transcriptional Regulators Abstract: DESCRIPTION (provided by applicant): Regulation of gene expression by transcription factors is one of the most fundamental biological processes. The pharmaceutical manipulation of this process would open doors toward new approaches to treatment of cancer and other major diseases. We aim to develop a novel, comprehensive technology for manipulation of gene expression based on synthetic analogues of eukaryotic transcription factors. The design and synthesis of these artificial transcription factors (ATFs) has been accomplished in Phase I by replacing functional domains of natural transcription factors with artificial chemical moieties. These ATFs have a remarkably high biological activity combined with novel properties resulting from their unique chemical composition and structure. In Phase II we propose to develop ATF technology further and apply it to target selected human genes in their native, chromosomal setting in tissue culture cells. This will be achieved by using a combination of chemical, biochemical, genetic and genomic tools. The specific aims of this proposal are: 1) Expanding the repertoire of ATFs with new chemical moieties. 2) Developing a robust and rapid assay for testing of ATFs in human cell culture lines. 3) Demonstration of the ability of ATFs to target selected endogenous human genes in tissue culture.
Thesaurus Terms:
gene induction /repression, genetic regulatory element, method development, peptide chemical synthesis, synthetic protein, transcription factor
genetic promoter element, peptide, protein binding, synthetic nucleic acid, transfection
polymerase chain reaction
Institution: CROSSLINK GENETICS CORPORATION 1 KENDALL SQ, BLDG 600, STE 255 CAMBRIDGE, MA 02139 Fiscal Year: 2003 Department: Project Start: 01-MAY-1998 Project End: 31-MAR-2005 ICD: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES IRG: ZRG1
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