Research Projects

Gene Therapy

Meet Dr. Leszek Lisowski ​ – Children’s Medical Research Institute & The University of Sydney

An all-in-one-gene therapy treatment for cystic fibrosis

Project Duration – 2 Years

Dr Leszek Lisowski is Head of the Translational Vectorology Unit at the Children’s Medical Research Institute (CMRI), and the sole recipient of the Cure4CF – Barbara Stow-Smith Cystic Fibrosis Innovation Grant for 2020.

As lead researcher, Dr Lisowski will be supported by his talented team of researchers, Dr Predag Kalajdzic from CMRI’s Vector and Genome Engineering Facility (VGEF), and two PhD students Adrian Westhaus and Kimberley Dilworth from CMRI, and his collaborator Professor Hiran Selvadurai who is Senior Staff Specialist in Paediatric Respiratory Medicine at The Children’s Hospital at Westmead.

Dr Lisowski’s project aims to develop new vector-based gene therapy tools for the treatment of Cystic Fibrosis.

Genetic diseases are caused by errors in our DNA and means some part of our body doesn’t function properly, leading to a life-threatening genetic disease like cystic fibrosis. The best way to treat or cure genetic diseases is to correct the problem at the source, to correct the DNA. That’s one of the approaches gene therapy takes to cure disorders.

Gene therapy works by inserting a gene with the correct DNA into a vector (in this case the vector that Dr Lisowski will be using is one called Adeno-Associated Viral vector, AAV), which is harmless but functions as a delivery vehicle that can go into the cells of a patient to deliver the therapeutic DNA payload and restore normal function of the mutated gene. This is already being used to treat diseases like haemophilia and spinal muscular atrophy.

More advanced technology being developed goes a step further, equipping these AAV vectors with the ability to scan billions of letters of the genetic code, find the single error causing a genetic disease, and precisely correct it in the patient’s DNA. In this case, the AAV delivers not only the healthy copy of the gene but also genes encoding highly sophisticated macromolecules that act like a microscopic scalpel, performing gene editing surgery on the DNA to cure a genetic disease.

Dr Lisowski’s project aims to develop two key tools:

  1. Novel AAV vectors for delivering functional copy of the genes to targeted cells within the body.
  2. Gene editing strategy to correct CF causing mutations in the fibrosis transmembrane conductance regulator (CFTR) gene.

Combination of those two novel technologies will form a powerful gene therapy approach, with the potential to cure cystic fibrosis.

Importantly, the success from this project will be directly applicable to many other genetic and acquired disorders of the lung, such as severe asthma, childhood interstitial lung disease (chILD) or Primary Pulmonary Hypertension (PHH).

The project will advance innovation in biomedical research and will develop technologies that will enable treatment of diseases that have a significant impact on society, it will also lead to the development of an original innovation/discovery.

“While the knowledge and diagnostic power around genetic disease have grown exponentially, the progress in disease prevention and treatment has been slower. Gene therapy has the power to fill that gap and to bring real benefits to patients. Our approach has the potential to alleviate the lung-associated complications of CF, which have major health implications and are usually the most difficult to treat”, says Dr Lisowski.




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