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AssigneePhenomix Corporation
InventorsRichard J. Glynne, Jesse Eunsuk Jun, Christopher Carl Goodnow
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The invention provides novel caspase recruitment domain 11 (CARD11), also known as CARMA-1, polypeptides, nucleic acids encoding them and methods for making and using them. In one aspect, the polypeptides of the invention have NFkB activating activity. The invention also provides non-human transgenic animals, e.g., mice, comprising the CARD11 nucleic acids of the invention. The invention also provides pharmaceutical compositions comprising a nucleic acid or polypeptide of the invention. Administration of a pharmaceutical composition of the invention to a subject is used to generate a toleragenic immunological environment in the subject. This can be used to tolerize the subject to an antigen. The invention also provides inbred mouse strains homozygous for a non-wild type CARD11 allele. This genotype results in mice having a phenotype comprising dermatitis, B cell defects and T cell defects.
An isolated or recombinant nucleic acid comprising a nucleic acid sequence having at least 90% sequence identity to SEQ ID NO:1, wherein the nucleic acid encodes at least one polypeptide having an NFkB activating activity.
An isolated or recombinant nucleic acid comprising a nucleic acid sequence having at least 90% sequence identity to SEQ ID NO:3.
An isolated or recombinant nucleic acid comprising a nucleic acid sequence having at least 90% sequence identity to SEQ ID NO:4.
A first nucleic acid molecule for identifying a second nucleic acid molecule, wherein the second nucleic acid molecule encodes a polypeptide with an NFkB activating activity, wherein the first nucleic acid molecule comprises at least 10 consecutive bases of a sequence as set forth in SEQ ID NO:1, SEQ ID NO:3 or SEQ ID NO:4, and further wherein the first nucleic acid molecule identifies the second nucleic acid molecule by binding or hybridization.
An expression cassette comprising a nucleic acid comprising a nucleic acid sequence having at least 90% sequence identity to SEQ ID NO:1, SEQ ID NO:3, or SEQ ID NO:4.
A vector comprising a nucleic acid comprising a nucleic acid sequence having at least 90% sequence identity to SEQ ID NO:1, SEQ ID NO:3, or SEQ ID NO:4.
The transformed cell of claim 14, wherein the cell is a bacterial cell, a mammalian cell, a fungal cell, a yeast cell, an insect cell or a plant cell.
A cloning vehicle comprising a nucleic acid sequence having at least 90% sequence identity to SEQ ID NO:1, SEQ ID NO:3, or SEQ ID NO:4.
An antisense oligonucleotide comprising a nucleic acid sequence complementary to or capable of hybridizing under stringent conditions to a nucleic acid sequence with at least 90% sequence identity to SEQ ID NO:1, SEQ ID NO:3, or SEQ ID NO:4.
A double stranded RNA oligonucleotide comprising a nucleic acid sequence complementary to or capable of hybridizing under stringent conditions to a nucleic acid sequence with at least 90% sequence identity to SEQ ID NO:1, SEQ ID NO:3, or SEQ ID NO:4.
A method of inducing the degradation by RNA interference of a message in a cell comprising administering to the cell or expressing in the cell a double stranded RNA molecule, or a molecule predicted to fold into a double stranded form, or two complementary RNA molecules that are capable of hybridizing to form a double stranded RNA molecule, wherein the double stranded RNA molecule comprises a nucleic acid sequence complementary to or capable of hybridizing under stringent conditions to a nucleic acid sequence at least 90% sequence identity to SEQ ID NO:1, SEQ ID NO:3, or SEQ ID NO:4.
An isolated or recombinant polypeptide comprising (i) an amino acid sequence having at least 95% sequence identity to SEQ ID NO:2;
A transgenic non-human animal comprising a heterologous nucleic acid, wherein the nucleic acid comprises a sequence having at least 90% sequence identity to SEQ ID NO:1 SEQ ID NO:3, or SEQ ID NO:4, wherein said animal exhibits a phenotype, relative to a wild-type phenotype comprising a characteristic selected from the group consisting of a dermatitis, a B cell defect, a T cell defect, and a combination of any two or more thereof.
A knockout non-human animal, wherein an endogenous gene sequence comprising a nucleic acid sequence having at least 90% sequence identity to SEQ ID NO:1 or SEQ ID NO:3 is disrupted so as to produce a phenotype comprising a characteristic selected from the group consisting of a dermatitis, a B cell defect, a T cell defect, and a combination of any two or more thereof.
An inbred mouse comprising a genome that is homozygous for a nucleic acid sequence encoding a polypeptide having at least 95% sequence identity to SEQ ID NO:2, wherein said polypeptide comprises a change in the amino acid sequence of SEQ ID NO:2 at amino acid residue number 298.
A method of treating an autoimmune disease or a lymphoma, said method comprising modulating a polypeptide having NFkB activating activity by administering a compound that binds to or modulates a polypeptide comprising (i) an amino acid sequence having at least 95% sequence identity to SEQ ID NO:2;
Dependencies are inferred from the claim text.