CF Gene Defect Corrected Using Molecular ‘Scissor’ Approach to Stem Cell Therapy in Early Study

CF Gene Defect Corrected Using Molecular ‘Scissor’ Approach to Stem Cell Therapy in Early Study

A new study suggests a method for correcting and improving stem cells derived from people with cystic fibrosis (CF), one that could lead to new ways of treating CF using a patient’s own cells. The report, titled Robust method for TALEN-edited correction of pF508del in patient-specific induced pluripotent stem cells, appeared Feb. 9, 2016, in the journal Stem Cell Research and Therapy.

CF is one of the most commonly occurring chronic diseases of the lungs in children and young adults. Breathing is often difficult for CF patients, due to a sticky mucus that builds up in the lungs and all too often leads to serious bacterial lung infections.

Mutations in the CFTR gene are the major cause of this mucus buildup. Scientists have identified over 2,000 mutations in the CFTR gene that are associated with the disease, which normally presents in patients at birth. CFTR, which stands for cystic fibrosis transmembrane conductance regulator, helps shuttle chloride ions in and out of cells, balancing salt and water in the cells that line the lungs.

The researchers, led by Maria Vicenta Camarasa of Caubet-Cimera Foundation, Hospital Joan March, in Spain, wanted to devise a method to genetically correct patient-derived stem cells. The investigators decided to correct the CFTR pF508del mutation in stem cells taken from CF patients, as this is the most frequent gene mutation that leads to CF, occurring in about two-thirds of all patients.

To change the gene, scientists used tiny molecular “scissors” known as TALENs, which stands for transcription activator-like effector nuclease. TALENs can cut and repair a faulty gene in a cell, and are able to target and cut specific genes, then repair them in a step-wise process. The researchers tested the new technology in fibroblasts (skin cells) taken from two different CF patients.

“Overall, the method described allows correction of patient-specific induced pluripotent cells in less than 3 months, and corrected cells have been directly cultured in a format which allows rapid scaling up for downstream applications,” they wrote in the report.

Based on standard laboratory measurements, including PCR DNA sequencing, the investigators were able to determine that the gene mutation was successfully corrected. They further noted that the method, based on the amount of time needed to complete the gene correction, could be practical for eventual clinical use.

Further work in studies of stem-cell transplantation in CF models and, eventually, humans is needed, however, to determine whether the technique could be successfully used to treat, or possibly cure, CF.

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