Research team to capitalize on benefits of genetic engineering
Cystic fibrosis (CF) is an often-fatal genetic disease that targets the digestive system and the lungs. Constant lung infection causes individuals diagnosed with CF to lose parts of their lungs, often resulting in the fatal damage of the lungs, leading to the loss of pulmonary function.
According to Cystic Fibrosis Canada (CFC), an estimated one in 3,600 children born in Canada is diagnosed with CF, while almost 4,000 Canadian children, adolescents, and adults are living with the disease.
However, thanks in part to researchers at the University of Guelph, the world might be one step closer to successfully treating CF. On March 6, according to a University of Guelph news release, pathobiology professor Sarah Wootton received $157,674 to study a method to permanently treat CF. The funding was awarded by CFC, a not-for-profit organization dedicated to the treatment and care of CF.
Wootton, who has been working on developing a lung-specific gene therapy vector to treat CF for over two years, found out about the CFC grant after a colleague gave a talk on the disease.
Professor Sarah Wootton, of the University of Guelph Pathobiology Department, recently received funding to research treatment for cystic fybrosis.
“Our lab has always had an interest in lung gene therapy, so when a talented postdoc named Jondavid de Jong joined the lab, we combined our expertise in lung gene therapy and baculovirus vectors (Bac) to develop a novel strategy to mediate integration of transgene cassettes into a known safe genomic location, leading to permanent transgene expression for the life of that cell,” explained Wootton.
The specific protein responsible for the development of CF is a mutated form of cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is a membrane protein – a protein that interact with membranes of cells – that ensures the movement of chloride and thiocyanate ions across epithelial cell membranes. The mutated form of CFTR leads to unregulated fluid movement in the lungs, pancreas, and other organs, leading to the development and diagnosis of CF.
What Professor Wootton hopes to accomplish with her research on permanent CFTR expression in airway epithelial cells is the maintenance and regulation of epithelial cells so they properly regulate epithelial fluid movement.
“The proposed work aims to directly address the cause of [CF] disease by developing a lung-specific gene therapy vector for permanent CFTR expression in airway epithelial cells,” said Wootton. “Additionally, evidence suggests that clinical benefits can be achieved through sustained expression of functional CFTR in as little as 10 to 25 per cent of lung cells.”
The transgene cassettes that carry the normal CFTR proteins are genetically manipulated viruses that will carry the proteins into lung cells. For those concerned about the nature of these viruses, Wootton confirms that there is little to worry about.
“Viruses have evolved to deliver genetic information to cells effectively,” explained Wootton in the March 6 news release. “We are taking advantage of the natural ability of a virus to target the lung and incorporating novel genome editing techniques into these vectors with the aim of permanently delivering functional genes to the lungs.”
According to Wootton, the virus “cannot [be replicated] in mammalian cells. You use it as a vehicle to deliver the DNA, and once inside the cell, it expresses the therapeutic protein, but cannot produce more of itself.”
Wootton is especially excited for the possibilities created by the manipulation and implementation of the Bac/site-specific nuclease vectors used in her team’s research. If Wootton’s research is successful, she expects to be able to use her team’s work to treat other genetic lung disorders.
“If successful, this Bac/site-specific nuclease platform could have the potential to permanently correct other genetic lung disorders, such as alpha-1-antitrypsin deficiency,” said Wootton. “The development of an AAVS1 [the viral integration site used to introduce the baculovirus vector] gene-targeting baculovirus vector allows us to capitalize on the strengths of baculovirus…”
For now, however, Wootton and her team are excited to continue working on their research.