Patent ID: 8715959
Filing Date: 2014-05-06
Classification: A61P,C07K,C12N,C12P

Abstract:
1. A recombinant gene expression modulation system comprising a recombinant gene expression cassette that is capable of being expressed in a host cell, said recombinant gene expression cassette comprising a polynucleotide that encodes a polypeptide comprising: i) a transactivation domain; ii) a DNA-binding domain that recognizes a response element associated with a gene whose expression is to be modulated; and iii) a nuclear receptor ligand binding domain comprising the amino acid sequence of SEQ ID NO: 1 wherein the amino acid sequence of SEQ ID NO: 1 has a) a single amino acid substitution mutation at amino acid residue 20, 21, 48, 51, 52, 55, 58, 59, 61, 62, 92, 93, 95, 96, 107, 109, 110, 120, 123, 125, 175, 223, 230, 234, or 238 of SEQ ID NO: 1; or b) a double amino acid substitution mutation at amino acid residues 95 and 110 of SEQ ID NO: 1, at amino acid residues 107 and 175 of SEQ ID NO: 1, at amino acid residues 127 and 175 of SEQ ID NO: 1, or at amino acid residues 107 and 127 of SEQ ID NO: 1; or c) a triple amino acid substitution mutation at amino acid residues 107, 127 and 175 of SEQ ID NO: 1, at amino acid residues 52, 107 and 175 of SEQ ID NO: 1, at amino acid residues 96, 107 and 175 of SEQ ID NO: 1, or at amino acid residues 107, 110 and 175 of SEQ ID NO: 1, wherein said nuclear receptor ligand binding domain is capable of binding a diacylhydrazine, and wherein said recombinant gene expression modulation system exhibits a different activity, in response to a ligand, relative to a gene expression modulation system that contains the nuclear receptor ligand binding domain of SEQ ID NO: 1 that does not comprise said substitution mutation.