BARBAS, CARLOS F., III,GOTTESFELD, JOEL M.,WRIGHT, PETER E.
申请号：
CA2291861
公开号：
CA2291861C
申请日:
1998.05.27
申请国别(地区):
CA
年份:
2013
代理人:
摘要：
Zinc finger proteins of the Cys2His2 type represent a class of malleable DNAbinding proteins which may be selected to bind diverse sequences. Typically,zinc finger proteins containing three zinc finger domains, like the murinetranscription factor Zif268 and the human transcription factort Sp1, bind ninecontiguous base pairs (bp). To create a class of proteins which would begenerally applicable to target unique sites within complex genomes, thepresent invention provides a polypeptide linker that fuses two three-fingerproteins. Two six-fingered proteins were created and demonstrated to bind 18contiguous bp of DNA in a sequence specific fashion. Expression of theseproteins as fusions to activation or repression domains allows transcriptionto be specifically up or down modulated within cells. Polydactyl zinc fingerproteins are broadly applicable as genome-specific transcriptional switchhesin gene therapy strategies and the development of novel transgenic plants andanimals. Such proteins are useful for inhibiting, activating or enhancing geneexpression from a zinc finger-nucleotide binding motif containing promoter orother transcriptional control element, as well as a structural gene or RNAsequence.
