Patent ID: 9051391
Filing Date: 2015-06-09
Classification: C07K,C12N

Abstract:
1. A cell expressing a non-natural T cell receptor (TCR), comprising: (i) recombinant nucleic acid sequences which encode exogenous α and β polypeptide chains that constitute the non-natural TCR and that correspond to the cell's endogenous α and β polypeptide chains that constitute the cell's natural TCR having a variable region and a constant region; and (ii) two siRNAs, one which inhibits the expression of the endogenous α polypeptide chain of the natural TCR and the other which inhibits the expression of the endogenous β polypeptide chain of the natural TCR by RNA interference, wherein: the expression of the endogenous α and β polypeptide chains of the natural TCR are inhibited by the siRNAs, the expression of the exogenous α and β polypeptide chains of the non-natural TCR, which partially differ in amino acid sequence from the endogenous α and β polypeptide chains of the natural TCR, are not inhibited by the siRNAs; and each of the nucleotide sequences encoding the exogenous α and β polypeptide chains is modified without changing the encoded amino acid sequence in a region of the polypeptide chain on which one of the siRNAs acts so that the region of the polypeptide chain encodes the same amino acid sequence in the exogenous polypeptide chain as in the corresponding endogenous polypeptide chain, and wherein the expression of each of the endogenous α and β polypeptide chains constituting the natural TCR is inhibited by RNA interference where the siRNAs target a sequence on mRNAs that encodes the constant region of each of the endogenous α and β polypeptide chains.