Researchers have harnessed the CRISPR-Cas9 technology to correct mutations in the blood stem cells of patients with a rare immunodeficiency disorder; the engineered cells successfully engrafted in mice for up to five months.

The study paves the way for CRISPR-Cas9 as a powerful gene editing tool with potential therapeutic applications for inherited diseases -- leading to more widely available gene therapy techniques. In particular, CRISPR-Cas9 holds promise for advancing ex vivo gene therapy, which tweaks disease-causing mutations in patient cells at the lab bench and implants them back into the body.

However, scientists' ability to selectively modify DNA errors without introducing additional mutations into a patient's genome remains a challenge. Suk See De Ravin and colleagues applied an ex vivo gene editing approach using the CRISPR-Cas9 platform to chronic granulomatous disease (CGD), a genetic disorder with limited treatment options that leads to life-threatening infections and often requires long-term antibiotics.

CGD is caused by defects in the NOX2 protein, a key molecule that helps the immune system destroy harmful bacteria. While stem cell transplantation offers a potential therapy for CGD, the procedure carries a risk of toxicity and potentially lethal complications.

The authors repaired the NOX2 mutation in stem cells from CGD patients, confirming their ability to differentiate into immune cells with restored antimicrobial function. When implanted into mice, the pool of altered cells maintained their gene edits long-term, with no signs of side effects. With further development, CRISPR-Cas9-based gene therapy may offer a new clinical strategy for CGD, and perhaps other blood disorders.