Gene Therapy for Cystic Fibrosis

The gene that produces the cystic fibrosis transmembrane conductance regulator (CFTR) protein is mutated in cystic fibrosis. To treat CF, scientists are investigating methods to supply an accurate copy of the gene.

Can Gene Therapy Help Cystic Fibrosis?

• DNA is a substance found in our cells that houses all the genetic information required to synthesise proteins. A gene is a particular DNA sequence that contains the instructions needed to make a protein.
• Non-integrating gene therapy involves delivering a segment of DNA containing a functional copy of the CFTR gene to a patient's cells; however, the DNA is not integrated into the genome and is not permanent.
• A segment of DNA containing the proper CFTR gene would be supplied to a patient's cells as part of integrated gene therapy. They would then have a permanent copy of the CFTR gene in their genome.

What Is Gene Therapy?

The instructions for producing the CFTR protein are found in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The synthesis of the CFTR protein may be impacted by a mutation, or change, in the genetic instructions. Mutations in the CFTR gene may cause an individual with cystic fibrosis to produce insufficient, no, or the wrong kind of protein. A series of issues affecting the lungs and other organs are brought on by each of these disorders.

Scientists have been searching for methods to fix the abnormalities in the CFTR gene that cause cystic fibrosis (CF) since the gene's discovery in 1989. Scientific discoveries within the last ten years have boosted the field of gene therapy, commonly referred to as gene transfer or gene replacement, even though development was originally slower than expected.

A new, corrected copy of the CFTR gene would be inserted into the patient's body's cells through a procedure known as gene therapy. The presence of the right copies of the CFTR gene would allow cells to produce normal CFTR proteins even though the mutant copies would still exist.

To show how this would function, watch this animation.

Types of Gene Therapy: Non-Integrating vs. Integrating

Two kinds of gene therapy could be used to treat cystic fibrosis. Which strategy will be most effective is still up in the air. Any successful gene therapy would need to overcome numerous obstacles in the process of physically delivering the technology to cells.

Non-Integrating Gene Therapy

Non-integrating gene therapy involves giving a patient's cells a fragment of DNA containing a functional copy of the CFTR gene; however, this DNA is not permanently incorporated into the genome. It's similar to slipping a fresh page in between the covers of an old book without binding it in place. The cell can use the new copy of the CFTR gene to produce normal CFTR proteins even while the gene therapy does not integrate into the genome.

Similar to how putting a new page just under a book's cover wouldn't affect the contents of the rest of the book, the non-integrating gene therapy strategy has the primary benefit of not disrupting the rest of the genome. This indicates that there is little chance of adverse effects, such as cancer. The transient nature of non-integrating gene therapy is a drawback. Gene therapy may only have a temporary effect that lasts a few weeks or months. Multiple treatments of gene therapy would likely be necessary for a patient with CF to benefit from it.

The U.S. Food and Drug Administration has approved non-integrating gene therapy to treat a rare form of blindness, and studies have demonstrated its efficacy in treating the blood clotting illness haemophilia. Patients with CF received a monthly dose of non-integrating gene therapy for a year as part of an English clinical trial. The study showed that lung function slightly improved and that CF gene therapy was safe. People with CF are presently participating in a clinical trial in the United States to investigate the safety and tolerance of non-integrating gene therapy.

Integrating Gene Therapy

A segment of DNA containing the proper CFTR gene would be supplied to a patient's cells as part of integrated gene therapy. Their genome, which is the complete collection of genetic instructions found in every cell, would then permanently contain the new copy of the CFTR gene. Gene therapy of this type is akin to appending a new page to an already published book.

Integrative gene therapy has the benefit of being permanent for the duration of the cell. This implies that a CF patient may only require gene therapy once or a few times throughout their lifetime. One drawback is that the location of the new CFTR gene copy's genomic integration may be less controllable. Similar to a new page being added at random to a book and upsetting a crucial chapter, the new copy might be introduced into a section of the genome that includes some crucial information. This implies that incorporating gene therapy may result in unfavourable side effects, such as a higher chance of developing cancer.

CAR-T therapy is one form of integrated gene therapy that has already received approval to treat specific types of lymphoma and leukaemia in individuals. Lab tests of integrating gene therapies to treat cystic fibrosis (CF) are underway, and over the next few years, a clinical trial evaluating the safety of this treatment strategy in CF patients may take place.