Gene-editing tool CRISPR may cure cystic fibrosis

The gene-editing technique CRISPR (pronounced crisper) is a powerful tool for altering DNA sequences and modifying gene function. It is a specialized segment of DNA that was adapted from a naturally occurring genome editing system found in bacteria. CRISPR allows researchers to edit genomes. Scientists can add, remove, or alter genes at a particular location in the genome. The CRISPR-Cas9 approach has generated a lot of excitement in the scientific community because of its efficiency, speed, accuracy, and low cost compared to other gene-editing approaches. However, scientists are concerned about the potential adverse effects of CRISPR because it involves cutting DNA. Now, scientists at the Netherlands’ Hubrecht Institute are working on a new approach which they believe is safer because it does not require the DNA to be cut. They believe this new technique can be applied to the mutation that leads to cystic fibrosis (CF). Cystic fibrosis is an inherited disease in which the lungs and digestive system are involved. People with CF have a gene mutation that causes them to produce thick mucus that obstructs the airways and clogs the pancreas. The disease is life-threatening and people with CF typically have a shorter-than-average lifespan. The new approach, base-editing, developed by the Hubrecht team can be applied to the CFTR gene that causes mucus buildup in cystic fibrosis patients. Traditionally, the enzyme Cas-9 is used to cut and replace a piece of mutated DNA. “With the new base-editing technique, the mutation in the CFTR gene can be detected and repaired without creating further damage in the genome,” said study co-author Maarten Geurts, a biologist at Hubrecht Institute. To demonstrate the technique, which was reported in the journal Cell Stem Cell, the scientists created a model of the digestive system from the stem cells of CF patients and performed base editing on these miniature guts to correct the CFTR mutation. Other researchers have proposed using CRISPR to target lung diseases, including a group at U Penn who applied CRISPR to animal models and inactivated a gene that causes lung disease. The biopharma community is excited about the prospects of the base editing approach. The startup Beam Therapeutics has applied it to diseases which are the result of point mutations, i.e., mutations that affect a single nucleoside base. The company has raised more than $300 million through funding and a public offering. Thus far, the base editing technique has shown great promise in treating diseases like sickle cell anemia that affect a single tissue or organ. However, there are challenges in using this technique to treat cystic fibrosis, warns Geurts, because the disease affects multiple organs. The Hubrecht group is planning further research to see how useful base editing can be for cystic fibrosis patients.