CF Foundation Award to Support Work Into Inhalable, Non-viral Gene Therapy

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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The Cystic Fibrosis Foundation (CFF) has awarded funding to enGene to support its work on a non-viral and inhalable gene therapy that could deliver a working copy of the CFTR gene to the lungs of people with cystic fibrosis (CF).

“Today’s announcement reflects yet another milestone on our path to delivering transformative therapies for people with CF,” William Skach, executive vice president and chief scientific officer of the CFF, said in foundation a press release.

“This is a very early but important step in advancing a viable way to produce healthy CFTR genes in the lungs,” he added. The award, whose amount was not disclosed, is part of the CFF’s $500 million Path to a Cure initiative that opened last year.

CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that codes for the CFTR protein. This protein controls the flow of chloride ions and water through cells that produce mucus, sweat, saliva, tears, and digestive enzymes.

These mutations cause CFTR to stop working properly, leading to the accumulation of thick and sticky mucus in organs that include the lungs.

Despite available therapies — including Trikafta (elexacaftor, tezacaftor, and ivacaftor) by Vertex Pharmaceuticals, approved in the U.S. in October 2019 and likely to treat most CF patients — some with specific CFTR mutations still lack effective therapies.

Moreover, a gene therapy could work regardless of the type of a patient’s mutations, and more than 1,700 disease-causing mutations in the CFTR gene are known.

Gene therapies today tend to use viruses engineered to be harmless — called vectors — as transport vehicles to deliver a working version of a gene to targeted cells. But these viral vectors can be recognized by the immune system and prompt a response.

enGene is developing a non-viral therapy designed to deliver a healthy CFTR gene directly to cells of the lungs.

Its approach couples the gene of interest to nanoparticles, called dually derivatized chitosan or DDX. These nanoparticles are coated with molecules that enhance their ability to penetrate tissues with a mucus barrier, like the lungs. The gene therapy is intended to inhaled and transported through the airways, reaching its targets while avoiding a risk of toxicities elsewhere in the body.

A non-viral, inhaled gene therapy would also make it easier to repeat the treatment, and to fine-tune dosing.

“enGene is developing a DDX-based inhalable formulation to carry DNA to the airways with the goal of functional complementation of CFTR mutations,” Jose Lora, CSO of enGene, said in a company press release. “We are thrilled to have the support of the Cystic Fibrosis Foundation to discover novel gene therapy candidates for patients with CF.”

The CFF award will be used by enGene to advance its therapies in preclinical testing.

Path to a Cure was established by the foundation to promote research into three ways of tackling the underlying cause of CF: repairing the non-functional CFTR protein, restoring CFTR protein when it’s missing, and fixing or replacing disease-causing mutations.

Because each approach requires specific knowledge and tools, CFF is bringing together researchers and industry leaders from varied fields of research.