The invention provides for DNA encoding Fas ligand muteins and chimeras and the proteins encoded thereby. The invention further includes the use of DNA and vectors to produce transformed cells expressing the mutant or chimeric Fas ligand. When the Fas ligand of the invention is a non cleavable form,
The invention provides for DNA encoding Fas ligand muteins and chimeras and the proteins encoded thereby. The invention further includes the use of DNA and vectors to produce transformed cells expressing the mutant or chimeric Fas ligand. When the Fas ligand of the invention is a non cleavable form, the cells expressing the Fas ligand are useful in vitro for identifying Fas expressing cells and in vitro or in vivo for reducing populations of Fas expressing cells. Thus, in other embodiments, the present invention is also directed to a method for treating a patient, for example a mammal, for autoimmune disease or transplant rejection by administering a Fas ligand therapeutic agent. The therapeutic agent is a polypeptide, a polynucleotide encoding the polypeptide or a small molecule. The polypeptides include full-length Fas ligand polypeptide, or a biologically active variant, derivative, portion, fusion or peptide thereof.
대표청구항▼
What is claimed: 1. A recombinant nucleic acid encoding a polypeptide comprising: a transmembrane domain of a cell surface protein; and a Fas ligand portion, wherein said Fas ligand portion comprises a sequence at least 90% homologous to SEQ ID NO: 8, and wherein the Fas ligand portion binds Fas an
What is claimed: 1. A recombinant nucleic acid encoding a polypeptide comprising: a transmembrane domain of a cell surface protein; and a Fas ligand portion, wherein said Fas ligand portion comprises a sequence at least 90% homologous to SEQ ID NO: 8, and wherein the Fas ligand portion binds Fas and induces apoptosis in cells that express Fas; wherein said polypeptide does not contain 17 contiguous amino acid residues starting at position 130 of SEQ ID NO: 12, is membrane bound when expressed in a mammalian cell and is resistant to cleavage by proteinases or convertases to release said Fas ligand portion. 2. The recombinant nucleic acid of claim 1, wherein said recombinant nucleic acid is operably linked to a promoter. 3. The recombinant nucleic acid of claim nucleic acid 1, wherein said transmembrane domain is an uncleavable transmembrane portion of a transmembrane protein other than pro-Fas ligand. 4. The recombinant nucleic acid of claim 1, wherein said polypeptide is a fusion protein. 5. A vector comprising the recombinant nucleic acid of claim 1. 6. The vector of claim 5, wherein said vector is a retroviral vector. 7. An isolated cell comprising the vector of claim 5, wherein said cell composes a non-cleavable Fas ligand on a surface of said cell. 8. The recombinant nucleic acid of claim 1, wherein said Fas ligand portion comprises SEQ ID NO:8. 9. The recombinant nucleic acid of claim 1, wherein the transmembrane domain is a transmembrane domain of a polypeptide selected from the group consisting of a membrane-bound antibody, a membrane bound viral antigen, and a member of the tumor necrosis factor receptor superfamily of polypeptides. 10. The recombinant nucleic acid of claim 9, wherein the transmembrane domain comprises a transmembrane domain of a tumor necrosis factor receptor superfamily polypeptide. 11. The recombinant nucleic acid of claim 10, wherein the tumor necrosis factor receptor superfamily polypeptide is selected from the group consisting of tumor necrosis factor receptor, CD30, nerve growth factor receptor, CD27, CD40, CD120a, CD120b, lymphotoxin beta receptor, and TRAIL recptor. 12. The recombinant nucleic acid of claim 1, wherein the transmembrane domain comprises a transmembrane domain of CD30 ligand. 13. The recombinant nucleic acid of claim 1, wherein the transmembrane domain comprises a transmembrane domain of CD40 ligand.
연구과제 타임라인
LOADING...
LOADING...
LOADING...
LOADING...
LOADING...
이 특허에 인용된 특허 (44)
Muzyczka Nicholas (Stony Brook NY) Hermonat Paul L. (Bethesda MD) Berns Kenneth I. (Mamaroneck NY) Samulski Richard J. (Princeton NJ), AAV transduction vectors.
Felgner Philip L. (Rancho Santa Fe CA) Wolff Jon A. (Madison WI) Rhodes Gary H. (Leucadia CA) Malone Robert W. (Chicago IL) Carson Dennis A. (Del Mar CA), Delivery of exogenous DNA sequences in a mammal.
Suni Jukka (Helsinki FIX) Vaheri Antti (Helsinki FIX), Human retrovirus-related products and methods of diagnosing and treating conditions associated with said retrovirus.
Huang Henry V. (University City MO) Levis Robin (Takoma Park MD) Rice Charles M. (University City MO) Schlesinger Sondra (University City MO) Shen Ping (University City MO) Xiong Cheng (St. Louis MO), Infectious Sindbis virus vectors.
Stephen Robert L. (2501 Kensington Ave. Salt Lake City UT 84108) Lugnani Franco (Viale Miramare 23 34135 Trieste ITX) Rossi Cino (Via Settala 32 00123 Roma ITX) Eruzzi Silvio (Via A. Mori ; 23 46100 , Intracorporeal iontophoretic method.
Vande Woude George F. (Berryville VA) McClements William L. (Silver Spring MD) Oskarsson Marianne K. (Bethesda MD) Blair Donald G. (Kensington MD), LTR-Vectors.
Goeddel David V. (Hillsborough CA) Rice Glenn C. (Palo Alto CA) Leung David W. H. (Foster City CA), Method for making variant secreted proteins with altered properties.
Dull Thomas J. (San Francisco CA) Riedel Heimo (San Francisco CA) Ullrich Axel (San Francisco CA), Novel receptors for efficient determination of ligands and their antagonists or agonists.
Axel Richard (New York NY) Wigler Michael H. (Cold Spring Harbor NY) Silverstein Saul J. (Irvington NY), Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials.
Lebkowski Jane S. (Portola Valley CA) McNally Maureen A. (Palo Alto CA) Okarma Thomas B. (Palo Alto CA), Production of recombinant adeno-associated virus vectors.
Lebkowski Jane S. (Portola Valley CA) McNally Maureen A. (Palo Alto CA) Okarma Thomas B. (Palo Alto CA), Production of recombinant adeno-associated virus vectors.
Schlesinger Sondra (St. Louis MO) Huang Henry V. (St. Louis MO) Levis Robin (Takoma Park MD) Weiss Barbara (Clayton MO) Tsiang Manuel (St. Louis MO), Sindbis virus vectors.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.