First-in-human pilot trial for new sickle cell disease gene therapy approach proves quicker, more efficient than industry average

FDA allows Boston Children's Hospital Expanded Access giving more patients with blood disorders opportunities to seek a cure

BOSTON, MA [Aug. 25, 2026] - Patients with sickle cell disease are often hesitant to undergo transformative gene therapy - the current lengthy process requires multiple hospital visits to collect enough stem cells. Researchers from Boston Children's Hospital have helped smooth the road to gene therapy with a new approach that collects enough of the patient's stem cells in a single hospital admission for most patients, improving the turnaround time for genetically altering and infusing the cells back into the patient. The long-term follow-up results of the first-in-human pilot phase I clinical trial are published recently in Blood.

Sickle cell disease is a genetic condition caused by a mutation in the adult form of hemoglobin, the protein in red blood cells that carries oxygen throughout the body. The hemoglobin mutations cause red blood cells to stiffen and change shape, which can result in pain, anemia, blood clots, strokes, organ damage, and premature death. Symptoms emerge after birth, when fetal hemoglobin is naturally turned off and adult hemoglobin takes over. This study works by collecting, modifying, and infusing a patient's own blood stem cells with instructions to restart healthy fetal hemoglobin production, while simultaneously shutting off the sickle cell gene.

Other U.S. Food and Drug Administration (FDA) approved commercial gene therapy technologies can require up to five sessions to successfully collect enough blood stem cells. In the new trial at Boston Children's, 10 of 11 participants had enough collected in a single session. Then, the stem cells from each participant in the pilot trial were genetically modified and cryopreserved at the Connell and O'Reilly Families Cell Manipulation Core Facility at the Dana-Farber Cancer Institute. After safety testing at the Boston Children's Therapeutic Innovation Laboratory, the genetically altered stem cells were infused back into patients with a turnaround time of an average of seven weeks compared to industry times that can take as long as six months or often longer. The report includes follow-up of patients for up to seven years after undergoing gene therapy.

"We have developed processes to overcome major barriers to transforming the lives of individuals with sickle cell disease with genetic therapies, and in our field that's very gratifying especially because this is based on scientific discovery made here at Children's," said David A. Williams, MD, chief of the Division of Hematology/Oncology at Boston Children's and President of the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, who along with Erica Esrick, MD, and John Manis, MD, led the research team. The approach was based on fundamental research also done at Boston Children's by Stuart Orkin, MD, and his laboratory.

"As a first-in-human ever trial for this approach, this result helps establish the most effective way to apply the process of collecting and engineering enough of the transplanted cells to guide a second, multi-site phase II trial that has now also completed full enrollment," says Williams.

Based on the safety findings of this pilot trial and the ongoing active phase II trial of an additional 25 participants, the FDA has approved extending the therapy through the Expanded Access Program which allows more patients to be treated before a formal Biological License Application (BLA) for drug approval. Additionally, the team licensed the technology to Caring Cross, a nonprofit dedicated to expanding access to cell and gene therapies globally, which is now opening trials in Brazil and India, home to large populations of people with sickle cell disease who could greatly benefit from the therapy.

Originally, Orkin co-discovered how fetal hemoglobin shuts off when red blood cells develop during a baby's first year of life. Williams' team then engineered an efficient process to reactivate the fetal hemoglobin gene and then moved that treatment to patients in a pilot study. Based on these results they have since expanded into a phase II pivotal multicenter national study.

Patients in the pilot trial did not experience unexpected safety events or any adverse effects related to the modification of stem cells used in the study.

Both trials were supported by the National Institutes of Health and the phase II study was also funded by the California Institute of Regenerative Medicine (CIRM) for individuals treated in California.

Thus far Boston Children's has treated 275 people with different types of gene therapy for various diseases.