The Cystic Fibrosis Foundation's unique research lab helps speed up the early steps of finding potential treatments that could fix or improve the faulty cystic fibrosis transmembrane conductance regulator (CFTR) protein that causes CF. The lab connects the discoveries made at academic institutions with the work needed by pharmaceutical companies to help turn those discoveries into new medicines.

To increase access to approved CFTR modulator therapies, researchers at the lab are testing cells with rare CFTR mutations to see how well they respond to the modulators elexacaftor/tezacaftor/ivacaftor (Trikafta) and vanzacaftor/tezacaftor/deutivacaftor (Alyftrek) — a process known as theratyping. If the lab tests are positive, that information is shared with the drug's manufacturer, who may use it to guide their work supporting the application to the U.S. Food and Drug Administration (FDA) for approval to treat additional mutations.

Since opening in 2012, the lab’s focus has expanded from developing new and better modulators to driving the next generation of transformative treatments, especially for people with rare and nonsense mutations who can’t use modulators. The lab now concentrates on developing or assisting in the development of transformative treatments — such as messenger RNA therapy, gene therapy, and gene editing — that offer the greatest hope for a future cure. 

Nonsense and Other Rare Mutations

More than 75% of the lab’s work is dedicated to identifying promising treatments that could benefit people with rare and nonsense mutations. 

Nonsense mutations (also known as “x” or “stop” mutations) cause cells to stop the production of the CFTR protein midway through the process, resulting in shortened, non-functional protein that the cell recognizes as defective and destroys. 

Lab researchers are exploring ways to promote the development of readthrough agents that can help the protein-making machinery of the cell “read through” or override premature stop signals so that a full-length CFTR protein can be made. To help further this research, the lab has collected cells from people with rare and nonsense mutations and is storing these cells in its cell bank. These cells are used at the lab for discovering and testing new treatment approaches and can also be requested by other researchers for their work. 

Genetic Therapies

Another key focus of the lab is furthering research into genetic therapies. One day they may be used to help all people with CF, but the lab — along with Foundation industry partners — initially will concentrate on developing these therapies for people who can’t be helped by modulators. 

Because of the large number of CFTR mutations, lab researchers are developing a blueprint for a potential therapy to insert a long section of DNA — known as a super exon — to correct most or all the mutations in the CFTR gene. This super-exon would override the faulty DNA and provide the correct instructions for lung cells in people with CF to produce a healthy CFTR protein and relieve CF symptoms in the lungs. (Read more about this gene editing approach.)

To support research into CF genetic therapies, the lab can host startups and other companies new to CF research for extended periods, as well as scientists from more established firms. Working alongside the lab’s experts in CF biology and testing techniques, industry researchers can gain training and mentorship that will help them conduct their work more effectively and accelerate the development of new treatments.