On May 19th Prime Medicine, an American biotech firm, announced the first use of pilot-edited technology to treat human patients. This represents a major breakthrough in gene editing, meaning the first clinical data to support the safety and efficacy of the technology.
The pioneering editing therapy, PM359, aims to correct the genetic mutations that cause Chronic granulomatous disease. Chronic granulomatous disease is a dangerous disease that disables many types of immune cells, including neutrophil.
An 18-year-old boy with Chronic granulomatous disease was given a single dose of PM359 intravenously. Data from Phase I and II studies showed that PM359 was well tolerated and rapidly implanted, and patients did not experience any serious side effects after one month of treatment.
At day 15,58% of patients had neutrophil NADPH oxidase activity, and at day 30,66% had neutrophil NADPH oxidase activity, exceeding the expected threshold of 20% clinical benefit is sufficient to significantly enhance the patient’s immune system.
In addition, the autologous Hematopoietic stem cell was rapidly implanted after myeloablative preconditioning. The neutrophil was confirmed on day 14, and the platelet was confirmed on Day 19. Notably, this rate was almost twice as fast as that of the approved gene-editing technology (with these same indicators, the median time to implantation of the approved gene-editing technology was Day 27 and Day 35, respectively) .
The findings were reported online the same day by nature, but have not been published in a peer-reviewed journal. Compared with CRISPR-Cas9 and base editing, lead editing is more versatile and predictable, with the ability to rewrite, embed or delete DNA fragments in a programmable manner, the report said. Chronic granulomatous disease is a good candidate for pilot editing because the most common types of mutations can be corrected by inserting two missing bases into the DNA sequence, this is beyond CRISPR-Cas9 and base editing.
The protocol for the lead-editing PM359 therapy involves taking a patient’s blood stem cells, editing them, and then injecting them back into the patient. This process adds to the cost and complexity of the treatment, as every patient treated must undergo a strict chemotherapy regimen that kills any remaining primordial stem cells before receiving the edited cells, make room for edited stem cells.