Scientists at Dana Farber/Boston Children's Blood Disorders
Centre and University of Massachusetts Medical School
The research study published in Nature Medicine
led by Scot Wolfe, Professor in the Department of Molecular, Cell and Cancer
Biology at UMass Medical School. The team collaborated with the Bauer
laboratory to improve the efficiency of delivery of CRISPR-Cas9 for therapeutic
gene editing of blood stem cells.
The team worked on making an efficient, effective targeted
edit. Previous research at Boston's children's hospital had indicated that inactivating
a gene called BCL11A can kick start the production of fetal hemoglobin.
BCL11A usually gets switched off when adult hemoglobin takes over after
similar to adult hemoglobin and does not sickle and restarting its production
can serve as a cure for SCD and beta-thalassemia
. The team at Bauer took this
further and found a genetic enhancer of BCL11A which is active only in blood
cells. This technique can enable efficient editing of autologous blood stem
cells collected from patients.
The gene edited cells when infused back into the
patients enabled the
production of normal blood cells.
technique was applied to the blood stem cells of patients with
beta-thalassemia, it generated enough hemoglobin to make up the shortfall.
The other study involving gene editing of beta-thalassemia
was published in the journal Blood.
The study involved nine patients who
donated their cells. These cells were manipulated in a petri dish. The CRISPR
system was able to make efficient edits and restored the normal
splicing of the beta-globin protein for normal production of hemoglobin.
The research team used a highly targeted enzyme Cas12a
to achieve greater efficiency and are keen to translate this
research into clinics. They plan to perform further studies with FDA approval
and are also seeking funding from the National Heart, Lung and Blood
Institute's Cure Sickle Cell initiative to start a clinical trial in patients.
Dana Farber has already been working on a gene therapy trial
for SCD. The research
team believes that a broad range of
therapeutic options is necessary to provide
patients with options of curatives.
- More efficient gene editing for blood stem cells could ease hemoglobin disorders - (https://vector.childrenshospital.org/2019/03/gene-editing-hemoglobin-disorders/)