Another method of treating sickle cell anemia
Stanford scientists have created a gene therapy to treat anemia
Stanford physicians have created a new type of gene therapy based on the CRISPR/Cas9 genomic editor, which "repairs" mutations in genes that turn red blood cells into crescent-shaped "crescents", which opens the way for the cure of anemia, according to an article published in the journal Nature (Dever et al., CRISPR/Cas9 β-globin gene targeting in human haematopoietic stem cells).
"We have spent more than five years trying to fix the beta-globin gene with the help of "old" genomic editing technologies. After a week of experiments with CRISPR, we surpassed the results that were obtained earlier," said Matthew Porteus from Stanford University (USA).
The CRISPR/Cas9 genomic editor, called the main scientific breakthrough of 2015, was created by American scientist Feng Zhang and a number of other molecular biologists about three years ago, and since then it has undergone several upgrades that allow scientists to use it to edit the genome with absolute accuracy.
Today, scientists are seriously considering the use of this technology for the treatment of congenital or genetically determined diseases – for example, muscular dystrophy, retinal pathologies, the first experiments on the treatment of which have already been carried out, as well as for the purification of the genome from HIV and other retroviruses.
Porteous and colleagues have developed a new type of therapy based on CRISPR/Cas9, which fights sickle cell anemia, a severe blood disease resulting from a mutation in one of the genes responsible for hemoglobin synthesis. As a result of one typo in the HBB gene, hemoglobin molecules in red blood cells deform, stretching them into a kind of "crescent", and lose their ability to normally carry oxygen.
Such changes lead to a lot of unpleasant consequences – the body is constantly experiencing oxygen starvation, the blood cells themselves are rapidly destroyed, which overloads the bone marrow and spleen, and the person himself constantly experiences pain, fatigue and suffers from inflammation and arthritis.
Stanford molecular biologists have found a way to save humans or animals from such torment by adapting CRISPR to fix this mutation in the HBB gene using a special retrovirus that infects blood stem cells.
Their gene therapy consists of three components – the CRISPR/Cas9 system, which cuts out the wrong section of the HBB gene that delivers it to the retrovirus cell and a special template from DNA that the cell uses to "fix" a break in the DNA chain generated by the genomic editor.
The scientists tested the work of this system on hematopoietic stem cells extracted from blood samples of laboratory mice and people suffering from anemia. In the end, Porteous and his colleagues managed to obtain cell cultures in which over 90% of the "blanks" of future erythrocytes contained a corrected version of the HBB gene.
Biologists transplanted these cells into the bone marrow of mice, purified from hematopoietic cells. As the experiment showed, the cells successfully survived this procedure and actively divided and turned into new blood cells even 14 weeks after their transplantation. This, according to scientists, opens the way for the use of CRISPR for the treatment of anemia, for which the appropriate infrastructure and methods of clinical application of CRISPR are being created at Stanford.
Interestingly, a similar but less effective technique for using CRISPR to remove a defective version of HBB was presented by another group of scientists from the University of Berkeley just a month ago. In both cases, geneticists managed to obtain a sufficient number of "correct" cells to achieve a therapeutic effect, which leaves hope that such procedures will find their place in medical practice soon enough.
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08.11.2016