摘要:
The present invention relates to novel fusion proteins which activate transcription, to nucleic acid constructs encoding the proteins and their use in the genetic engineering of cells. Key fusion proteins of the invention contain at least two mutually heterologous domains, one of which being a bundling domain. Bundling domains include any domain that induces proteins that contain it to form multimers ('bundles') through protein-protein interactions with each other or with other proteins containing the bundling domain. Examples of bundling domains that can be used in the practice of this invention include domains such as the lac repressor tetramerization domain, the p53 tetramerization domain, a leucine zipper domain, and domains derived therefrom which retain observable bundling activity. Cells are engineered by the introduction of recombinant nucleic acids encoding the fusion proteins, and in some cases with additional nucleic acid constructs, to render them capable of ligand-dependent regulation of transcription of a target gene. Administration of the ligand to the cells then regulates (positively, or in some cases, negatively) target gene transcription.
摘要:
This invention concerns new configurations for biological switches and provides new methods and materials useful for regulating biological events in animal cells. The invention involves recombinant DNA constructs comprising DNA sequences derived from sequences encoding the proteins FRAP, Tor1, Tor2 and other proteins capable of binding to FKBP:rapamycin, other recombinant DNA constructs comprising DNA sequences encoding part or all of an FKBP protein, the proteins encoded by those constructs, cells (especially animal cells) transformed with one or more of the constructs, small molecules (multivalent multimerizing agents) which bind to and are capable of inducing multimerization of the chimeric proteins, and methods for preparing and using the foregoing.
摘要:
This invention provides novel materials and methods involving the heterologous expression of transcription factors which are useful for effecting transcription of target genes in genetically engineered cells or organisms containing them. Target gene constructs and other materials useful for practicing the invention are also disclosed.
摘要:
Materials and methods are disclosed for regulation of biological events such as target gene transcription and growth, proliferation or differentiation of engineered cells.
摘要:
This invention concerns new configurations for biological switches and provides new methods and materials useful for regulating biological events in animal cells. The invention involves recombinant DNA constructs comprising DNA sequences derived from sequences encoding the proteins FRAP, Tor1, Tor2 and other proteins capable of binding to FKBP:rapamycin, other recombinant DNA constructs comprising DNA sequences encoding part or all of an FKBP protein, the proteins encoded by those constructs, cells (especially animal cells) transformed with one or more of the constructs, small molecules (multivalent multimerizing agents) which bind to and are capable of inducing multimerization of the chimeric proteins, and methods for preparing and using the foregoing.