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Sickle Cell Disease (SCD) is an inherited blood disorder that leads to the production of abnormal hemoglobin. Ordinarily, the hemoglobin protein, which lives inside red blood cells, attaches to oxygen in the lungs and is carried to all parts of the body. Normal red blood cells are flexible and can move easily through blood vessels. When a person has sickle cell disease, a gene mutation distorts red blood cells into a crescent or sickle shape. These sickles can block red blood cells from passing through blood vessels and delivering oxygen to organs and tissues. Symptoms include anemia, hypertension, organ damage — along with excruciating pain.

Meet Manny

He is the first patient to participate in a clinical trial testing a novel gene therapy approach for treating SCD. After needing monthly blood transfusions for 17 years to control his disease, he is now symptom-free.

Read his story
Clinician holds stethoscope to Manny's chest

How gene therapy for SCD works

All babies in the womb and newborns have a certain version of hemoglobin called fetal hemoglobin. Even babies with sickle cell disease make normal red blood cells because fetal hemoglobin doesn't sickle. But shortly after birth, the body stops making fetal hemoglobin — its production blocked by the expression of the BCL11A gene — and starts making adult hemoglobin. The reason this is critical for sickle-cell patients is that the gene mutation causing the disease is on the adult hemoglobin gene, not the fetal hemoglobin. Gene therapy in sickle cell works by knocking down the expression of the BCL11A gene to flip the switch back to fetal hemoglobin, simultaneously increasing fetal hemoglobin, which does not sickle, and directly reducing sickling hemoglobin. 

To perform gene therapy, a patient’s blood stem cells are collected and exposed to a vector containing instructions to knock down BCL11A. The patient then receives chemotherapy in a process called conditioning, likened to plowing a field to make room for new seeds. Finally, the gene-modified cells are given back via intravenous infusion.

Sickle cell disease gene therapy clinical trial

Pilot and Feasibility Study of Hematopoietic Stem Cell Gene Transfer for Sickle Cell Disease
Recruiting children and adults ages 3 to 40 Years (full eligibility criteria)
Boston Children’s Hospital
Started: Feb. 2018
Principal investigators: David A. Williams, MD, and Erica Esrick, MD 
Colleen Dansereau, MSN, RN, CPN617-919-7008 or

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