Difference between revisions of "Part:BBa K4421002"

Revision as of 02:26, 21 June 2022

iCasp9

iCasp9 is a chemically-inducible kill switch.When exposed to a synthetic dimerizing drug such as AP1903, the inducible caspase 9 (iCasp9) becomes activated and leads to the rapid death of cells expressing this construct.iCasp9 can be activated by AP1903 that has proven safe at the required dose for optimum deletional effect

Usage and Biology

iCasp9 is based on a modified human caspase 9 fused to a human FK506 binding protein (FKBP) to allow conditional dimerization using a small molecule pharmaceutical.

A single 10-nM dose of synthetic dimerizer drug induces apoptosis in 99% of transduced cells selected for high transgene expression in vitro and in vivo.

This system has several advantages over currently available suicide genes. First, it consists of human gene products with low potential immunogenicity. Second, administration of dimerizer drug has no effects other than the selective elimination of transduced T cells. Third, inducible caspase 9 maintains function in T cells overexpressing antiapoptotic molecules. These characteristics favor incorporation of inducible caspase 9 as a safety feature in human T-cell therapies.

Sequence and Features