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CRISPR-Cas9 gene editing is expected to treat sickle cell anemia and β-thalassemia
CRISPR-Cas9 gene editing is expected to treat sickle cell anemia and β-thalassemia. Today, after more than 70 years, advanced gene editing technology can provide molecular therapy. Every year, 60,000 people worldwide are diagnosed with severe beta thalassemia and 300,000 people are diagnosed with sickle cell disease.
In 1949, Linus Carl Pauling (Linus Carl Pauling) discovered that sickle cell anemia is a “molecular disease” due to the variation of hemoglobin, indicating that human genetic diseases are caused by the expression of mutant genes Abnormal proteins put forward the concept of molecular disease for the first time. This laid the foundation for examining hereditary mutations at the molecular level and made him the originator of molecular biology.
PS: Linus Carl Pauling (Linus Carl Pauling) was born in 1901, received his doctorate in 1925, became the youngest professor at the California Institute of Technology in 1931, and was elected to the American Academy of Sciences in 1933, the youngest academician in history . He is full of personality and innovative spirit, constantly pioneering edge disciplines, and has made outstanding achievements in many fields of chemistry. He is the greatest chemist of the 20th century.
Sickle cell anemia (SCA) is the most common inherited blood disease in the United States. Approximately 72,000 Americans are affected or have a probability of 1 in 500 among African Americans. SCA is a disease characterized by pain, chronic hemolytic anemia, and severe infection. It usually starts in childhood. Until now, there is no cure. The combination of fluids, analgesics, antibodies, and blood transfusions are often used in clinical treatment.
News from Nature on December 8th, after more than 70 years, today, advanced gene editing technology can provide molecular therapy. Researchers report the successful treatment of sickle cell anemia and β-thalassemia using another gene editing method.
In the New England Journal of Medicine, the research team reported on the results of two promising pioneering gene therapy trials for the underlying cause of sickle cell anemia. The purpose of both is to promote the production of another form of hemoglobin (called fetal hemoglobin). A study conducted this study using CRISPR-Cas9 genome editing, which provides an important proof of the concept of this technology: the first published instructions for using a gene editing system to treat genetic diseases.
Another method uses RNA to change the expression of fetal hemoglobin genes. Both therapies free participants from the “pain crisis” caused by sickle cell disease.
The two clinical trials only recruited a small number of participants, and it is still too early to say how long the effect will last. The first participant in the RNA study received treatment two and a half years ago. The CRISPR-Cas9 method has also been used to treat patients with a serious related genetic disease called β-thalassemia, and these participants do not need blood transfusions that normally require control of the disease.
Marina Cavazzana, a gene therapy researcher at the Necker Children’s Hospital in Paris, said this is very promising. We need new technology and more than one product on the market is needed to face the huge problem of sickle cells.
Sickle-shaped anemia (SCD) is similar to β-thalassemia, and both are the two most common genetic diseases caused by mutations in a single gene (β subunit mutation). Both of these conditions will affect the production of β-globin, a component of hemoglobin. People with severe β-thalassemia suffer from anemia; in sickle cell anemia, blood cells deform, clump, and block blood vessels, sometimes depriving tissues of oxygen and causing pain.
Both diseases can be cured by bone marrow transplantation, although most people with this disease cannot find a suitable donor. But in recent years, various experimental gene therapy methods have suddenly appeared. Last year, the European Union approved a gene therapy called Zynteglo to treat beta thalassemia. This method uses a virus to transfer a copy of the functional β-globin gene to hematopoietic stem cells. Bluebird Bio, a biotechnology company in Cambridge, Massachusetts, is also conducting similar clinical trials in patients with sickle cell disease.
Gene editing therapy is expected to become a new treatment option
The CRIPSR and RNA methods have adopted different strategies. They tried to promote the expression of a type of hemoglobin, which is normally produced in the fetus and then disappears soon after birth. The researchers hypothesized that turning fetal hemoglobin back on could compensate for the defective β-globin in patients with sickle cell anemia and β-thalassemia.
Both studies show that this is indeed the case. One of the research groups, including researchers from Vertex Pharmaceuticals in Boston, Massachusetts, and CRISPR Therapeutics in Cambridge, Massachusetts, used CRISPR–Cas9 to change a gene region called BCL11A, which is required to prevent fetal hemoglobin. produce. Through the inactivation of this gene, the research team hopes to restore the production of fetal hemoglobin in adult red blood cells.
Another group of researchers led by David Williams, a hematologist at Boston Children’s Hospital and Bluebird Bio researchers, used a small piece of RNA to shut down the expression of the BCL11A gene in red blood cells.
David Altshuler, chief scientific officer of Vertex, said that a paper related to CRISPR-Cas9 gene editing therapy reported data from two participants, one with beta thalassemia and the other with sickle cell disease. A total of 10 people have been treated in the trial.
At the same time, Williams’ paper reported data from six patients with sickle cell disease, and his trial later treated three more patients.
So far, participants with beta thalassemia do not require blood transfusions, and participants with sickle cell disease have not reported pain episodes since treatment. The side effects of these therapies—including infection and abdominal pain—are temporary and are related to the treatment needed to prepare the bone marrow for surgery.
Current limitations of gene editing therapy
In both cases, blood stem cells are removed from the bone marrow and then reinjected into the patient after being modified. But before these cells are reintroduced, participants will receive medication to ablate the remaining blood stem cells. This treatment is difficult and risky, and it puts the patient at risk of infection until the bone marrow is restored, and may impair fertility. Researchers are now looking for a gentler method to prepare for this injection of bone marrow.
David Rees, an expert in hematology at King’s College Hospital in London, said that until these therapies become safer, these methods may be limited to patients with serious illnesses who do not respond to other medications. Scientifically speaking, these studies are quite exciting. But in the long run, it is difficult to become a mainstream treatment.