Modified caspase polypeptides and uses thereof

摘要

The technology relates in part to compositions comprising modified Caspase-9 polypeptides, compositions comprising nucleic acids coding for modified Caspase-9 polypeptides, chimeric modified Caspase-9 polypeptides, and methods of use thereof, including methods for cell therapy. Methods for cell therapy include modifying transfused cells to express an inducible modified Caspase-9 protein, with reduced basal activity in the absence of the inducer.

主权项

1. A composition comprising a nucleic acid comprising a nucleotide sequence that encodes a chimeric protein comprising a FKBP multimeric ligand binding region and a modified Caspase-9 polypeptide, wherein the modified Caspase-9 polypeptide comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 9, and comprises the amino acid substitution N405Q, wherein
a) the chimeric protein has a basal activity less than 50% of the basal activity of a chimeric protein comprising a FKBP multimeric ligand binding region and a Caspase-9 polypeptide lacking the caspase recruitment domain (CARD) and having the amino acid sequence of SEQ ID NO: 9; and b) Caspase-9 activity is induced upon binding of a ligand to the FKBP multimeric ligand binding region of the chimeric protein.