Mini-guts grown in the lab using cystic fibrosis patients' cells can help pinpoint those who are most likely to benefit from new drugs, according to a new study. The findings pave the way to exploiting so-called organoids as a tool for screening drugs and personalizing treatment for patients with cystic fibrosis and other genetic diseases. Cystic fibrosis, a condition in which sticky mucus clogs the lungs and other organs, is caused by mutations in the CFTR channel. CFTR-targeting therapies have recently been approved to treat cystic fibrosis, but identifying the subset of patients most likely to respond to these drugs remains challenging, time-consuming, and costly. To better predict individuals' clinical response, Johanna Dekkers and colleagues grew gut organoids, three-dimensional adult stem cell cultures that resemble the gut, using rectal biopsies from 71 cystic fibrosis patients who carried a wide range of CFTR mutations. The researchers found that the mini-guts' responses to CFTR-targeting drugs in vitro closely correlated with published data from clinical trials of the same drugs. Based on these findings, they selected two individuals with rare CFTR mutations whose rectal organoids responded strongly to the treatment. Indeed, when given the drug, both individuals showed fewer disease symptoms and improved lung function. Altogether, the results support the potential to use patient-derived organoids to tailor treatments for individuals.