The ability to edit genes in patients’ blood
stem cells — which produce red blood cells, platelets, immune cells and more — offers
the potential to cure many genetic blood disorders. If all goes well, the
corrected cells engraft in the bone marrow and produce healthy, properly
functioning blood cells… forever.
But scientists have had difficulty introducing
edits into blood stem cells. The efficiency and specificity of the edits and
their stability once the cells engraft in the bone marrow have been variable.
A new approach, described this week in Nature Medicine and in January in the journal Blood, overcomes prior technical challenges, improving the efficiency, targeting and durability of the edits. Researchers at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and the University of Massachusetts Medical School successfully applied the technique to two common blood diseases — sickle cell disease and beta thalassemia — involving mutations in the gene for beta globin protein.
New tools and technologies fueled biomedicine to great heights in 2017. Here are just a few of our top picks. All are great examples of research informing better care for children (and adults).
1. Gene therapy arrives
In 2017, gene therapy solidly shed the stigma of Jesse Gelsinger’s 1999 death with the development of safer protocols and delivery vectors. Though each disease must navigate its own technical and regulatory path to gene therapy, the number of clinical trials is mounting worldwide, with seven gene therapy trials now recruiting at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. In August, the first gene therapy won FDA approval: CAR T-cell therapy for pediatric acute lymphoblastic leukemia. …
Gene editing has begun to be tested in clinical trials, using CRISPR-Cas9, zinc finger nucleases (ZFN) and other technologies to directly edit DNA inside people’s cells. Multiple trials are in the recruiting or planning stages. But a study in PNAS this week raises a note of caution, finding that person-to-person genetic differences may undercut the efficacy of the gene editing process or, in more rare cases, cause a potentially dangerous “off target” effect.
The study adds to evidence that gene editing may need to be adapted to each patient’s genome, to ensure there aren’t variants in DNA sequence in or near the target gene that would throw off the technology. …
Three-dimensional modeling and CRISPR-Cas9 gene editing technology are giving scientists a new view into Sturge-Weber syndrome, a rare congenital disorder that causes small blood vessels, called capillaries, to be malformed. These capillary malformations can cause port wine birthmarks on the face and neck, and in some cases, abnormal vasculature in the brain that can spark seizures.