VitaSeno by Aubrai
As we age, our bodies accumulate senescent, or “zombie", cells which are highly damaged, yet refuse to die. They disrupt tissue homeostasis, are toxic to neighboring cells and are associated with numerous age-related diseases. This project will utilize CRISPR gene-editing technology to find genes that are essential for keeping senescent cells alive, thus providing new drug targets to selectively eliminate them.
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Summary
Synthetic lethality is the phenomenon whereby inactivation of either gene A or B is tolerable, yet the loss of both is lethal. Synthetic lethality screens have helped discover novel drug targets for cancer therapy i.e. PARP inhibitors. Numerous proteins have been discovered to be down-regulated during senescence, so I propose that synthetic lethality screens should be applied to longevity research to discover new drug targets to selectively kill senescent cells.
Problem
Removal of senescent cells in animal models can delay age-related diseases and increase lifespan, although no “senolytic” therapies are yet available for humans.
Impact
Finding genes which are essential for senescent cell survival will allow the development of new therapies to tackle senescence - one of the key hallmarks of ageing.
Market Overview
Additional Documentation
Summary
Synthetic lethality is the phenomenon whereby inactivation of either gene A or B is tolerable, yet the loss of both is lethal. Synthetic lethality screens have helped discover novel drug targets for cancer therapy i.e. PARP inhibitors. Numerous proteins have been discovered to be down-regulated during senescence, so I propose that synthetic lethality screens should be applied to longevity research to discover new drug targets to selectively kill senescent cells.
Problem
Removal of senescent cells in animal models can delay age-related diseases and increase lifespan, although no “senolytic” therapies are yet available for humans.
Impact
Finding genes which are essential for senescent cell survival will allow the development of new therapies to tackle senescence - one of the key hallmarks of ageing.
Generate a monoclonal CRISPR knock-out cell line
Infect WT and KO cells with a full genome CRISPR KO library
Synthetic Lethality full genome CRISPR KO drop-out screen
Genomic DNA isolation and PCR-based library prep
Next-generation sequencing and data analysis
Validate hits for senolytic potential
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