Cystic Fibrosis

Disease Background

Cystic fibrosis (CF) is a genetic disease that affects the tissues that produce mucous secretions. Patients with the disease produce abnormally thick, sticky mucus in their airways. This is due to the faulty transport of sodium (salt) and chloride from within the cells' lining organs (such as the lungs and pancreas) to their outer surfaces. The thick mucus obstructs the airways and also allows the growth of bacteria that can cause hard-to-treat infections. In addition, the mucus obstructs the pancreas, preventing enzymes that are needed to help break down and digest food from reaching the intestines.

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Cystic fibrosis (CF) affects approximately 30,000 children and adults in the United States, and more than 10 million people are carriers of the defective gene responsible for the condition but have no symptoms. An individual must inherit a defective copy of the CF gene from each parent to develop CF. Each time two carriers conceive a child, there is a 25 percent chance that the child will have CF, a 50 percent chance that the child will be a carrier and a 25 percent chance that the child will have two normal CF genes.

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Our Research

Overview of Hutchinson Center Research

Hutchinson Center research on cystic fibrosis largely focuses on developing effective treatments that are based on the delivery of healthy copies of CF genes into patients, whose cells possess two abnormal copies of the gene. This approach, known as gene therapy, often involves engineering harmless viruses to serve as delivery agents, or vectors, of the healthy gene. Hutchinson Center researchers helped to pioneer this method, which led to the first successful applications of gene therapy in humans.

In the case of cystic fibrosis, a modified virus based on an adeno-associated virus was discovered to be a potentially effective vector for delivery of healthy genes to the airway cells involved in cystic fibrosis. A particular type of adeno-associated virus identified at the Hutchinson Center works particularly well to transfer genes to mouse lung, and researchers are currently working to extend this work to treatment of human patients.

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Basic biology of retroviruses and parvoviruses

At the dawn of the biotechnology revolution, when scientists had first discovered ways to recombine DNA, one of the first dreams of the new technology was to cure genetic diseases like cystic fibrosis, thalassemia and hemophilia as well as some cancers by transferring corrective genes into cells. This technique is also known as gene therapy.

One of the first researchers to successfully transfer genes into a cell was Hutchinson Center researcher Dr. Dusty Miller, who used a disabled virus to make the transfer. This technology continues to provide scientists around the world with the tools to develop and extend knowledge into gene therapy.

Today, research in Miller's laboratory focuses on the basic biology of two types of viruses with the goal of developing more efficient viral transport vehicles, known as vectors, for human gene therapy. The development of gene therapy depends on understanding cell biology, gene transfer technology, and the biology of disease.

Collaborations with Drs. Hans-Peter Kiem and Robert Andrews have led to significant improvements in gene transfer using retroviral vectors based on an animal virus that uses a cell surface receptor that is prevalent on the surface of blood-making stem cells. The ability to transfer genes into these cells is critical to achieving long-term integration of curative genes for a variety of diseases, including certain cancers.

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Relevant Articles

• Pushing the envelope on gene-therapy research — Human Biology Division study of sheep tumor virus may lead to new model for understanding effective gene therapy
  
  
• Miller, Riddell play key roles in UW gene therapy project
  
  
• Insight into lung cancer — Sheep virus supplies clues in Dusty Miller laboratory
  
  

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