Nucleic acid vectors comprising DNase I hypersensitive sites

US6022736A · kind A · utility

Assignees

• THE UAB RESEARCH FOUNDATION · US
• The Trustees of the University of Pennsylvania · US
• The Board of Regents of the University of Washington · US

Inventors

• Tim Townes · Birmingham, US
• Thomas Ryan · Birmingham, US
• Richard D. Palmiter · Seattle, US
• Ralph L. Brinster · Gladwyne, US
• Richard R. Behringer · Philadelphia, US

Key dates

• Filing date: Jun 6, 1995
• Grant date: Feb 8, 2000
• Expiry date: Jun 6, 2015

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y10S435/948
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The present invention provides novel recombinant nucleic acid vectors which may be used to produce .alpha.-globin as well as other proteins of interest in quantity in the red blood cells of transgenic animals or cell cultures of erythroid lineage. The present invention also provides for the transgenic animals which contain these recombinant nucleic acid vectors. The vectors of the invention comprise at least one of the major DNase I hypersensitivity sites associated with the .beta.-globin locus together with a gene of interest. According to various embodiments of the invention, the vectors may be used to create transgenic animals or to transfect cells in culture. In a specific embodiment of the invention, a vector which comprises two DNase I hypersensitivity sites together with the human .alpha.-globin gene is used to create transgenic animals which produce human .alpha.-globin protein in erythroid tissues, including red blood cells. In a preferred specific embodiment of the invention, transgenic animals are created which comprise human .alpha.-globin and .beta.-globin genes, each under the transcriptional influence of two .beta.-globin locus DNase hypersensitivity sites; these tra…