Claims
- 1. A molecule comprising a DNA sequence encoding a polypeptide which is capable of binding to RIP and modulating or mediating the intracellular activity of RIP, which polypeptide is:
(a) a RIP-associated protein (RAP) encoded by said DNA sequence in a clone deposited with collection Nationale de Cultures de Microorganisme under the accession number 1-2706; (b) a fragment of (a) which is capable of binding to RIP or inhibiting the NF-κB inducing effect of RIP; or (c) an analog of (a) or (b) which differs from the sequence of (a) or (b) by no more than 10 substitutions, deletions and/or insertions of amino acid residues and is capable of binding to RIP or inhibiting the NF-κB inducing effect of RIP.
- 2. A molecule according to claim 1, wherein said DNA sequence encodes a RAP protein having the amino acid sequence of SEQ ID NO: 2.
- 3. A molecule according to claim 1, comprising the sequence of SEQ ID NO: 1.
- 4. A molecule in accordance with claim 1, wherein said DNA sequence is:
(i) the cDNA sequence of SEQ ID NO: 1; or (ii) a DNA sequence which encodes the amino acid sequence encoded by the DNA sequence of (i).
- 5. A molecule in accordance with claim 1 which is a vector.
- 6. A vector according to claim 5 capable of expressing the polypeptide encoded therein in a eukaryotic host cell.
- 7. A vector according to claim 5 capable of expressing the polypeptide encoded therein in a prokaryotic host cell.
- 8. Transformed eukaryotic or prokaryotic host cells containing a vector according to claim 5.
- 9. A method for producing a polypeptide capable of binding to RIP and modulating or mediating the intracellular activity of RIP, comprising growing the transformed host cells according to claim 8 under conditions suitable for the expression of said polypeptide, effecting post-translational modifications as necessary for obtaining said polypeptide and isolating said expressed polypeptide.
- 10. A pharmaceutical composition for modulating the RIP effect on cells, comprising, as active ingredient, a recombinant animal virus vector encoding a protein capable of binding a cell surface receptor and encoding the RAP protein encoded by a DNA sequence in a clone deposited with Collection Nationale de Cultures de Microorganismes under accession number I-2706.
- 11. A method of modulating processes that are mediated/modulated by RIP directly or indirectly and which include the inhibition of NF-κB and JNK, comprising treating said cells with one or more polypeptides capable of binding to RIP, wherein said treating of cells comprises introducing into cells a DNA sequence encoding said one or more polypeptides in the form of a suitable vector carrying said sequence, said vector being capable of effecting the insertion of said sequence into said cells in a way that said sequence is expressed in said cells, and said one or more polypeptides being selected from the group consisting of:
(a) a RIP-associated protein (RAP) encoded by a DNA sequence in a clone deposited with Collection Nationale de Cultures de Microorganismes under accession number I-2706; (b) a fragment of (a) which is capable of binding to RIP or inhibiting the NF-κB inducing effect of RIP; and (c) an analog of (a) or (b) which differs from the sequence of (a) or (b) by no more than 10 substitutions, deletions and/or insertions of amino acid residues and is capable of binding to RIP or inhibiting the NF-κB inducing effect of RIP.
- 12. A method for the modulation or mediation of the RIP modulated/mediated intracellular effects on the inflammation, cell death or cell survival pathways in which RIP is involved directly, or indirectly via other modulators/mediators of these pathways, comprising treating cells with one or more polypeptides, wherein said treating of cells comprises introducing into said cells a DNA sequence encoding said polypeptide in the form of a suitable vector carrying said sequence, said vector being capable of effecting the insertion of said sequence into said cells in a way that said sequence is expressed in said cells, and said one or more polypeptides being selected from the group consisting of:
(a) a RIP-associated protein (RAP) encoded by a DNA sequence in a clone deposited with Collection Nationale de Cultures de Microorganismes under accession number I-2706; (b) a fragment of (a) which is capable of binding to RIP or inhibiting the NF-κB inducing effect of RIP; and (c) an analog of (a) or (b) which differs from the sequence of (a) or (b) by no more than 10 substitutions, deletions and/or insertions of amino acid residues and is capable of binding to RIP or inhibiting the NF-κB inducing effect of RIP.
- 13. A method according to claim 12, wherein said treating of said cells is by transfection of said cells with a recombinant animal virus vector comprising:
(a) constructing a recombinant animal virus vector carrying a sequence encoding a viral surface protein (ligand) that is capable of binding to a specific cell surface receptor on the surface of said cells to be treated and a second sequence encoding said polypeptide, that when expressed in said cells is capable of modulating/mediating the activity of RIP; and (b) infecting said cells with said vector of (a).
- 14. A method for treating tumor cells or HIV-infected cells or other diseased cells, comprising:
(a) constructing a recombinant animal virus vector carrying a sequence encoding a viral surface protein capable of binding to a specific tumor cell surface receptor or HIV- infected cell surface receptor or receptor carried by other diseased cells and a sequence encoding a polypeptide, that when expressed in said tumor, HIV-infected, or other diseased cell is capable of enhancing the RIP modulated/mediated direct or indirect killing of said cell, wherein said one or more polypeptides are selected from the group consisting of:
(a) a RIP-associated protein (RAP) encoded by a DNA sequence in a clone deposited with Collection Nationale de Cultures de Microorganismes under accession number I-2706; (b) a fragment of (a) which is capable of binding to RIP or inhibiting the NF-κB inducing effect of RIP; and (c) an analog of (a) or (b) which differs from the sequence of (a) or (b) by no more than 10 substitutions, deletions and/or insertions of amino acid residues and is capable of binding to RIP or inhibiting the NF-κB inducing effect of RIP.
Priority Claims (1)
Number |
Date |
Country |
Kind |
IL 120485 |
Mar 1997 |
IL |
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CROSS REFERENCE TO RELATED APPLICATION
[0001] The present application is a divisional of application Ser. no. 09/927,458, which is a continuation-in-part of application Ser. no. 09/381,358, filed Sep. 20, 1999, now abandoned, which is a 371 national stage application of PCT/IL98/00125, filed Mar. 19, 1998, the entire contents of Ser. Nos. 09/927,458 and 09/381,358 being incorporated herein by reference.
Divisions (1)
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Number |
Date |
Country |
Parent |
09927458 |
Aug 2001 |
US |
Child |
10245593 |
Sep 2002 |
US |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
09381358 |
Sep 1999 |
US |
Child |
09927458 |
Aug 2001 |
US |