Terry Horgan, from Montour Falls, New York, was enrolled in the study in late August with the hope of treating Duchenne muscular dystrophy (DMD).
The 27-year-old was one of the first Americans to be treated with CRISPR - which works by editing genes by precisely cutting DNA and letting the natural repair process take over.
His rare genetic muscle-wasting disease is caused by a mutation in the gene needed to produce a protein called dystrophin.
As of now, the exact cause of Horgan's death last month remains unclear.
But his death is raising questions about the overall prospect of gene-editing therapies, which have buoyed hopes among many families facing rare and incurable diseases.
At this point, it's unclear whether Horgan received the treatment and whether CRISPR, other aspects of the study or the disease itself contributed to his death.
Deaths are not unheard of in clinical trials, which test experimental treatments and sometimes involve very sick people.
But trials involving CRISPR are relatively new. And Fyodor Urnov, a CRISPR expert at the Innovative Genomics Institute at University of California, Berkeley, said any death during a gene therapy trial is an opportunity for the field to have a reckoning.
'Step one is to grieve for the passing of a brave human soul who agreed to be basically a participant in an experiment on a human being,' Urnov said. 'But then, to the extent that we can, we must learn as much as we can to carve out a path forward.'