F508-del CFTR rescue by mutated toxoids and evaluation of its functional efficacy in vivo

Many genetic diseases caused by small genetic mutations do not result in complete loss of protein fnction, but rather are due to the degradation of mutant protein by a “quality control” mechanism (endoplasmic reticulum-associated degradation-ERAD) soon after it is made. Prominent amongst such ERAD-dependent diseases is Cystic Fibrosis(CF), a chronic, progressive, life-threatening genetic disease that primarily affects the lung, gastrointestinal and reproductive systems. Certain bacterial and plant toxins “hijack” this “quality control” system in the ER. Our cell culture results show inactivated (detoxified) Cholera Toxoid rescues the mutant protein causing cystic fibrosis from degradation. This could be a new basis for the treatment of many of the genetic diseases caused by ERAD. Animal studies will allow the partner company to bring this novel therapy to the market faster. To remain competitive in the global economy, corporations need to accelerate pipeline development by outsourcing specific research projects.

Faculty Supervisor:

Dr. Christine Bear

Student:

Humaira Adnan

Partner:

ERAD Therapeutics

Discipline:

Biology

Sector:

Life sciences

University:

University of Toronto