CRISPR edits to stimulate healthier hemoglobin could prove sickle cell cure

Besides being a benign genetic condition, the hereditary persistence of fetal hemoglobin could, with some help from CRISPR, lead to a new treatment for common blood disorders, such as sickle cell anemia and beta-thalassemia.

Sickle cell and beta-thalassemia are caused by genetic mutations in a component called “beta” that is present only in adult hemoglobin, said St. Jude Children’s Research Hospital, which led the research, in a statement. Individuals start showing symptoms after birth, as adult hemoglobin gradually replaces fetal hemoglobin.

Fetal hemoglobin does not have “beta” components and have “gamma” subunits instead, St. Jude said. And so, the genetic mutations that cause these disorders do not affect fetal hemoglobin. It has long been known that blocking the “gamma-to-beta” switching of hemoglobin components can increase the levels of fetal hemoglobin in adults, thus alleviating sickle cell and beta-thalassemia symptoms, according to the statement.

“Our work has identified a potential DNA target for genome editing-mediated therapy and offers proof-of-principle for a possible approach to treat sickle cell and beta-thalassemia,” said Dr. Mitchell Weiss, chair of St. Jude’s Department of Hematology, in the statement. The team “snipped” out the target using CRISPR, removing a short section of DNA that drives “gamma-to-beta” switching and resulting in “sustained” elevated levels of fetal hemoglobin in adult red blood cells, Weis said. They worked on blood cells isolated from patients with sickle cell and beta-thalassemia, and were able to generate red blood cells with enough fetal hemoglobin to be healthy, the statement said.

“Using genome editing to restore the hereditary persistence of fetal hemoglobin is an attractive possibility, because it can be achieved relatively easily using current technologies,” Weiss said.

While it’s an appealing possibility, the researchers caution there’s much refinement to be done before clinical trials can be considered. They want to perfect the gene-editing process to avoid off-target effects that could potentially be harmful.

- here's the statement
- read the study abstract

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