Targeted and inducible cell killing by combinatorial expression of recombinant caspase subunits

Columbia University Science & Technology Ventures
posted on 12/23/2008

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Problem or Unmet Need

While proper cellular apoptosis (cell death) is absolutely critical in the prevention of many forms of cancer, control and manipulation of this ubiquitous apoptotic pathway as a developing therapeutic strategy in cancer patients is hampered by leaky, non-specific, and potentially toxic side-effects.

Details of the Invention

This invention offers a tightly controlled method to induce apoptosis in specific cells at a specific time by generating an active caspase (a key apoptotic-inducing protein) only when two separate promoters are each induced. The apoptotic pathway can then be turned off in a similarly specific manner by expression of a caspase-neutralizing protein controlled by a third promoter.

Cancer ablation therapy Research tool
o High throughput screening for novel anti-apoptotic cellular proteins or compounds
o Generation of animal clones ablated for a specific cell type or tissue
o Temporal ablation of specific cells to study their role in development and/or behavior

Provides a general method for the reconstitution of all known caspases
o This allows for a broad selectable spectrum of apoptotic pathway targets High degree of apoptotic specificity in targeting a specific cell type Tight regulation and expression of apoptotic induction at a specific time point The three above points together provide a highly accurate, more specific and less leaky apoptosis-inducing mechanism