Scientists Examine CRISPR as a Therapeutic Approach for Treating Blood Disorders

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A new study reveals a potential new approach to treat sickle cell disease and beta thalassemia using CRISPR-Cas9 gene-editing technology.

A group of scientists have developed a potential new approach to treat common blood disorders by using CRISPR-Cas9 gene-editing technology. In a new study published on August 15, 2016 in Nature Medicine, scientists led by a group of researchers from St. Jude Children’s Research Hospital, say they have identified a possible DNA target for genome editing that could be used to treat sickle cell disease and beta thalassemia.

In the Nature study, researchers performed CRISPR-Cas9 genome editing of human blood progenitors. According to the study, scientists edited human-blood progenitors in an attempt to mutate “a 13-nt sequence that is present in the promotors of the [hemoglobin subunit gamma 1] HBG1 and [hemoglobin subunit gamma 2] HBG2.” The edited progenitors produced red blood cells with higher levels of fetal hemoglobin, enough to stop the morphing of red blood cells that occur with sickle cell disease, thereby returning them to their natural state.

The use of CRISPR-Cas9 provides a potentially viable option for reversing gamma-to-beta switching of hemoglobin subunits, which researchers indicate is effective for increasing the levels of fetal hemoglobin in patient’s red blood cells. For patients with sickle cell disease and beta thalassemia, the gamma subunits in fetal hemoglobin can more effectively transfer oxygen through the blood compared to the beta subunits in adult hemoglobin.

“Several techniques have emerged in recent years that use gene editing to manipulate hematopoietic stem cells for the treatment of blood disorders. Some of them use artificial restriction enzymes like zinc finger nucleases, another method exploits structural changes that can be introduced into chromatin, and others, including our method, involve CRISPR gene editing,” study author Mitchell J. Weiss, MD, PhD, chair of the Hematology Department at St. Jude told Pharmaceutical Technology. “Each of these approaches is different and none have been tested in clinical trials in humans. Our approach uses CRISPR-Cas9 to disrupt the mutated genes and restore fetal hemoglobin levels in hematopoietic stem cells. It remains to be established which is the best and safest approach to gene editing for patients with sickle cell disease.”

According to Weiss, some other methods that may prove effective for treating blood disorders include the correction of sickle cell-associated mutations by using zinc finger nuclease enzymes, a method that produces the “forced looping” of chromatin, and a method that uses CRISPR-Cas9 to target BCL11A, which inhibits expression of fetal hemoglobin in adults. While many of these methods show promise as potential treatments for blood disorders, Weiss acknowledges that they have not yet been tested in clinical trials.


“Our study is a proof-of-principle that our gene-editing approach can be successful in isolated blood-forming stem cells. Further work is needed to improve the gene editing process and to ensure that no off-target mutations arise with this approach,” Weiss continued. “More research is definitely needed before moving this work towards the clinic. What would be beneficial is a head-to-head comparison of the merits of each of the gene editing processes that have been proposed to date. It is likely to be some time before any of these approaches are tested in a clinical trial but the potential is clearly there.”

The use of CRISPR-Cas9 technology has been a highly debated topic in the scientific community as early human trials are set to begin. In July 2016, scientists at Sichuan University’s West China Hospital in Chengdu announced plans to begin the first human trial using CRISPR technology, Nature reported. The scientists plan to begin the trial in patients with metastatic non-small cell lung cancer in August 2016. Researchers in the United States have also made strides toward bringing CRISPR-Cas9 to clinical trials. In June, a panel from the National Institutes of Health approved the first US clinical trial for CRISPR-Cas9 to test whether or not the technique is safe for use in humans. According to Nature, the small study will examine CRISPR-Cas9 in 18 patients with different types of cancer.

Source: Nature Medicine