CRISPR and the Cure Frontier

Stuart Orkin, MD ’72

David G. Nathan Distinguished Professor of Pediatrics, HMS

HHMI Investigator, Boston
Children’s Hospital

Vijay Sankaran, MD ’09, PhD ’10

Jan Ellen Paradise, MD Professor of Pediatrics, HMS

Stuart Orkin, MD ’72, David G. Nathan Distinguished Professor of Pediatrics at HMS and HHMI Investigator at Boston Children’s Hospital, and his lab led the research that made CASGEVY—the world’s first FDA-approved CRISPR gene therapy for sickle cell disease—possible. The lab showed that sickle cell disease disrupts adult hemoglobin but leaves fetal hemoglobin unaffected, which the body normally stops producing at maturity. Working with then-student Vijay Sankaran, MD ’09, PhD ’10—now the Jan Ellen Paradise, MD Professor of Pediatrics at HMS—along with NIH patient samples and collaborators in Italy, Orkin identified BCL11A, the gene that controls the body’s switch from fetal to adult hemoglobin production. Their 2008 paper in Science opened new directions in sickle cell research.

Five years later, Orkin lab member Daniel Bauer, MD, PhD, found a key DNA sequence in BCL11A that controls its activity. From there, another of Sankaran’s professors, David Altshuler, MD ’94, PhD ’94, and his team at Vertex Pharmaceuticals transformed these discoveries into CASGEVY, marking a new era in gene therapy. In 2026, Orkin received the Breakthrough Prize for this body of work.