Gene Therapy for Cystic Fibrosis

Cystic fibrosis is caused by mutations in the gene responsible for producing the cystic fibrosis transmembrane conductance regulator (CFTR) protein. For this reason, scientists are exploring ways to provide a correct copy of the gene to treat CF.

6 min read
In this article
Summary
  • Our cells contain DNA, a molecule that stores all the genetic information needed to make proteins. A gene is a specific sequence of DNA that carries the instructions for making a protein.

  • In integrating gene therapy, a piece of DNA that contains a correct version of the CFTR gene would be delivered to an individual's cells. The new copy of the CFTR gene would then become a permanent part of their genome.

  • In non-integrating gene therapy, a piece of DNA with a correct copy of the CFTR gene is delivered to an individual's cells, but the DNA remains separate from the genome and is not permanent.

What Is Gene Therapy?

The cystic fibrosis transmembrane conductance regulator (CFTR) gene contains the instructions for making the CFTR protein. When there is a mutation — or alteration — in the genetic instructions, the production of the CFTR protein may be affected. In people with cystic fibrosis, mutations in the CFTR gene can result in no protein, not enough protein, or the protein being made incorrectly. Each of these defects leads to a cascade of problems that affect the lungs and other organs.

Since the discovery of the CFTR gene in 1989, scientists have been trying to find ways to correct the mutations in the gene that cause CF. Although progress was initially slower than anticipated, scientific breakthroughs in the past 10 years have accelerated advances in gene therapy, also known as gene transfer or gene replacement.

Gene therapy is a process in which a new, correct version of the CFTR gene would be placed into the cells in a person's body. Although the mutant copies of the CFTR gene would still be there, the presence of the correct copies would give cells the ability to make normal CFTR proteins.

Watch this animation to see how this might work.

Types of Gene Therapy: Integrating vs. Non-Integrating

There are two types of gene therapy that have potential to treat CF. It is not yet clear which option will work best. The process of physically delivering gene therapy technology to cells is full of challenges that would have to be overcome for any gene therapy to work.

To learn more about these challenges, watch this video:

Integrating Gene Therapy

In integrating gene therapy, a piece of DNA that contains a correct version of the CFTR gene would be delivered to an individual’s cells. The new copy of the CFTR gene would then become a permanent part of their genome, which is the entire set of genetic instructions that is in every cell. This kind of gene therapy is like binding a new page into an existing book.

An advantage of an integrating gene therapy is that it is permanent for the life of the cell. This means that a person with CF might have to receive the gene therapy only once or a few times in their life. A disadvantage is that there may be limited control over where the new copy of the CFTR gene integrates into the genome. The new copy could be inserted into a part of the genome that contains some critical information, like the new page being randomly added to a book and disrupting an important chapter. This means integrating gene therapy could have undesirable side effects, such as increasing the risk of cancer.

A type of integrating gene therapy, known as CAR-T therapy, has already been approved to treat patients with certain kinds of leukemia and lymphoma. Integrating gene therapies to treat CF are being tested in the lab, and a clinical trial to test the safety of this approach in people with CF could happen in the next several years.

Non-Integrating Gene Therapy

In non-integrating gene therapy, a piece of DNA with a correct copy of the CFTR gene is provided to an individual's cells, but the DNA remains separate from the genome and is not permanent. This is like placing a new page between the covers of an existing book without permanently attaching it. Even though the gene therapy does not become part of the genome, the cell can still use the new copy of the CFTR gene to make normal CFTR proteins.

A major advantage of the non-integrating gene therapy approach is that it does not disrupt the rest of the genome, just like adding a new page right under the cover of a book would not disturb the contents of the rest of the book. That means that the risk of side effects, including cancer, is low. A disadvantage of non-integrating gene therapy is that it is not permanent. The effect of the gene therapy might last only for several weeks or months. A person with CF would probably need to be treated with the gene therapy repeatedly for it to be effective.

Non-integrating gene therapy has been approved by the U.S. Food and Drug Administration to treat a rare type of blindness, and it has also been shown to work in studies for hemophilia, a blood clotting disorder. In a clinical trial in England, people with CF were given a dose of a non-integrating gene therapy once per month for a year. The study indicated that the CF gene therapy was safe and resulted in a small improvement in lung function. A clinical trial in the U.S. is currently studying the safety and tolerability of non-integrating gene therapy in people with CF.

To learn more about several key types of lung cells that could be targeted by genetic therapies, including gene therapy, watch this video.

Share this article
Topics
Genetic Therapies | Research
Downloads
Understanding Genetic Therapies Download PDF
Questions to Ask Before Enrolling in a Genetic Therapy Trial Download PDF
Genetic Therapies for CF - Glossary of Key Terms Download PDF
Have questions? We’re here to help. Call us at 1-800-FIGHT CF

(1-800-344-4823)
Mon - Thu, 9 am - 7 pm ET
Fri, 9 am - 3 pm ET

 

More Ways To Get Help