Researchers from the Leibniz-Forschungsinstitut für Molekulare Pharmakologie and Charité – Universitätsmedizin Berlin have developed a nanobody that repairs the defective CFTR protein causing cystic fibrosis in approximately 90 percent of patients.
How the nanobody corrects the CFTR defect
The nanobody, a tiny antibody fragment, enters human cells and stabilizes the misfolded CFTR protein at position 508 where a single amino acid is missing in the F508del mutation. This allows the chloride channel to reach the cell membrane and regulate salt and water transport in lung tissue, preventing the buildup of thick mucus that leads to chronic infections and lung function decline. The study, led by Luise Franz of FMP and Tihomir Rubil of Charité, was published in Nature Chemical Biology.
Current treatments exit gaps this approach could fill
Existing triple therapy with elexacaftor, tezacaftor and ivacaftor raises CFTR function to about 50 percent of normal but often fails to resolve chronic lung inflammation and does not work for all patients. Professor Marcus Mall of Charité’s pediatric pneumology team noted that while the triple therapy has improved treatment, persistent inflammation and intolerance remain issues for some. The nanobody targets the root folding defect directly, potentially offering a complementary or alternative option for those unresponsive to or ineligible for modulator drugs.
What researchers say about next steps
Professor Christian Hackenberger of Leibniz-FMP, whose team designed the nanobody, emphasized that the molecule was developed in laboratory settings and requires further testing before clinical use. The approach focuses on intracellular correction of CFTR, a mechanism distinct from current modulators that act primarily at the cell surface. No timeline for human trials or regulatory submission was provided in the source material.
What is cystic fibrosis and how common is the F508del mutation?
Cystic fibrosis, also known as CF, is a genetic disorder caused by defects in the CFTR gene that disrupts salt and water balance in the lungs and other organs. The F508del mutation, involving the loss of one amino acid at position 508 of the CFTR protein, occurs in about 90 percent of cystic fibrosis patients.
How does a nanobody differ from a regular antibody?
A nanobody is a smaller, stable fragment of an antibody that can bind precisely to specific protein surfaces and, unlike conventional antibodies, can penetrate human cells to act intracellularly.
