Jeffrey Mcintyre Voss

US Patent:

6783756, Aug 31, 2004

Filed:

Mar 30, 1999

Appl. No.:

09/281674

Inventors:

Hermann Bujard - Heidelberg, DE
Manfred Gossen - El Cerrito CA
Jochen G. Salfeld - North Grafton MA
Jeffrey W. Voss - West Boylston MA

Assignee:

Abbott GmbH Co., KG - Wiesbaden

International Classification:

A61K 6300

US Classification:

424 9321, 514 44, 435455, 435465

Abstract:

A method for regulating expression of a tet operator-linked gene in a cell of a subject is disclosed. In one embodiment, the method involves introducing into the cell a nucleic acid molecule encoding a tetracycline-controllable transactivator (tTA), the tTA comprising a Tet repressor operably linked to a polypeptide which directly or indirectly activates transcription in eucaryotic cells; and modulating the concentration of a tetracycline, or analogue thereof, in the subject. Alternatively, in another embodiment, the method involves obtaining the cell from the subject, introducing into the cell a first nucleic acid molecule which operatively links a gene to at least one tet operator sequence, introducing into the cell a second nucleic acid molecule encoding a tTA, to form a modified cell, administering the modified cell to the subject, and modulating the concentration of a tetracycline, or analogue thereof, in the subject. The first and second nucleic acid molecule can be within a single molecule (e. g. , in the same vector) or on separate molecules.

US Patent:

20020086426, Jul 4, 2002

Filed:

Feb 5, 2001

Appl. No.:

09/777317

Inventors:

Hermann Bujard - Heidelberg, DE
Manfred Gossen - El Cerrito CA, US
Jochen Salfeld - North Grafton MA, US
Jeffrey Voss - West Boylston MA, US

Assignee:

BASF Aktiengesellschaft - Ludwigshafen

International Classification:

C12N015/00

US Classification:

435/440000

Abstract:

A method for regulating expression of a tet operator-linked gene in a cell of a subject is disclosed. In one embodiment, the method involves introducing into the cell a nucleic acid molecule encoding a tetracycline-controllable transactivator (tTA), the tTA comprising a Tet repressor operably linked to a polypeptide which directly or indirectly activates transcription in eucaryotic cells; and modulating the concentration of a tetracycline, or analogue thereof, in the subject. Alternatively, in another embodiment, the method involves obtaining the cell from the subject, introducing into the cell a first nucleic acid molecule which operatively links a gene to at least one tet operator sequence, introducing into the cell a second nucleic acid molecule encoding a tTA, to form a modified cell, administering the modified cell to the subject, and modulating the concentration of a tetracycline, or analogue thereof, in the subject. The first and second nucleic acid molecule can be within a single molecule (e.g., in the same vector) or on separate molecules.

US Patent:

20020152487, Oct 17, 2002

Filed:

Jun 25, 2001

Appl. No.:

09/892227

Inventors:

Hermann Bujard - Heidelberg, DE
Manfred Gossen - El Cerrito CA, US
Jochen Salfeld - North Grafton MA, US
Jeffrey Voss - West Boylston MA, US

Assignee:

BASF Aktiengesellschaft

International Classification:

A01K067/027
A61K031/65

US Classification:

800/014000, 800/015000, 800/016000, 800/017000, 800/018000, 514/152000

Abstract:

Transgenic animals carrying two transgenes, the first coding for a transactivator fusion protein comprising a tet repressor and a polypeptide which directly or indirectly activates in eucaryotic cells, and the second comprising a gene operably linked to a minimal promotor operably linked to at least one tet operator sequence, are disclosed. Isolated DNA molecules (e.g., targeting vectors) for integrating a polynucleotide sequence encoding a transactivator of the invention at a predetermined location within a second target DNA molecule by homologous recombination are also disclosed. Transgenic animals having the DNA molecules of the invention integrated at a predetermined location in a chromosome by homologous recombination are also encompassed by the invention. Methods to regulate the expression of a tet operator linked-gene of interest by administering tetracycline or a tetracycline analogue to an animal of the invention are also disclosed. The regulatory system of the invention allows for conditional inactivation or modulation of expression of a gene of interest in a host cell or animal.

US Patent:

58889817, Mar 30, 1999

Filed:

Jun 7, 1995

Appl. No.:

8/479306

Inventors:

Hermann Bujard - Heidelberg, DE
Manfred Gossen - El Cerrito CA
Jochen G. Salfeld - North Grafton MA
Jeffrey W. Voss - West Boylston MA

Assignee:

BASF Aktiengesellschaft - Ludwigshafen
Knoll Aktiengesellschaft - Ludwigshafen

International Classification:

A61K 4800
C12N 1500

US Classification:

514 44

Abstract:

A method for regulating expression of a tet operator-linked gene in a cell of a subject is disclosed. In one embodiment, the method involves introducing into the cell a nucleic acid molecule encoding a tetracycline-controllable transactivator (tTA), the tTA comprising a Tet repressor operably linked to a polypeptide which directly or indirectly activates transcription in eucaryotic cells; and modulating the concentration of a tetracycline, or analogue thereof, in the subject. Alternatively, in another embodiment, the method involves obtaining the cell from the subject, introducing into the cell a first nucleic acid molecule which operatively links a gene to at least one tet operator sequence, introducing into the cell a second nucleic acid molecule encoding a tTA, to form a modified cell, administering the modified cell to the is subject, and modulating the concentration of a tetracycline, or analogue thereof, in the subject. The first and second nucleic acid molecule can be within a single molecule (e. g. , in the same vector) or on separate molecules.

US Patent:

62521365, Jun 26, 2001

Filed:

Sep 29, 1998

Appl. No.:

9/163269

Inventors:

Hermann Bujard - Heidelberg, DE
Manfred Gossen - El Cerrito CA
Jochen G. Salfeld - North Grafton MA
Jeffrey W. Voss - West Boylston MA

Assignee:

BASF Aktiengesellschaft
Knoll Aktiengesellschaft

International Classification:

C12N 1509
C12N 1582
C12N 1587
C12N 1590
A01H 500

US Classification:

800278

Abstract:

Transgenic animals carrying two transgenes, the first coding for a transactivator fusion protein comprising a tet repressor and a polypeptide which directly or indirectly activates in eucaryotic cells, and the second comprising a gene operably linked to a minimal promoter operably linked to at least one tet operator sequence, are disclosed. Isolated DNA molecules (e. g. , targeting vectors) for integrating a polynucleotide sequence encoding a transactivator of the invention at a predetermined location within a second target DNA molecule by homologous recombination are also disclosed. Transgenic animals having the DNA molecules of the invention integrated at a predetermined location in a chromosome by homologous recombination are also encompassed by the invention. Methods to regulate the expression of a tet operator linked-gene of interest by administering tetracycline or a tetracycline analogue to an animal of the invention are also disclosed. The regulatory system of the invention allows for conditional inactivation or modulation of expression of a gene of interest in a host cell or animal.