CRISPR to cure sickle cell disease, editing the patient’s own stem cells for the treatment
Earlier this decade, scientists had developed an efficient gene-editing tool by modifying the natural immune machinery in bacteria. They manipulated the Cas9 enzyme in bacteria to insert or delete genes in the genome.
Sickle cell disease
The scientists at the Institut Imagine in Paris, France, were studying the potential of CRISPR to cure the genetic sickle cell disease.
Proteins called hemoglobin in the blood that transports oxygen are malfunctioned in this disease. A particular mutation in the bone marrow stem cells leads to the withered and hardened red blood cells, poor in carrying oxygen.
Dr. Tristan Felix, whose laboratory is part of the GENE FOR CURE
project, led by Professor Marina Cavazzana, based at the institute, said that they are using CRISPR-Cas9 technology to delete some genes in the patient’s genome.The researchers took the stem cells from the patient’s body, rectified the faulty genes causing sickle cell disease using CRISPR-Cas9, and then reinserted them back to the body.
Dr. Felix’s research uses CRISPR-treated stem cells to restart making fetal hemoglobin, the oxygen-carrying protein in red blood cells. While it’s usually made when a child is in the womb, it offers a good substitute for adult hemoglobin.
They used the CRISPR-Cas9 technology to delete the gene that ‘switches off’ the expression of fetal hemoglobin, thereby allowing it to be produced again. Once the stem cells are reinserted into the bone marrow, they start producing healthy red blood cells with fetal hemoglobin.
Currently, the new treatment is being tested in animals, but the scientists behind this discovery believe that the new treatment will work well along with other sickle cell medicines. This new treatment will help the medical field to cure patients with sickle cell disease completely.
The surgical reinsertion of stem cells to the bone marrow is risky and requires an extended stay at the hospital even after the surgery. Also, there is no guarantee for long term success yet.
Since the treatment involves the use of CRISPR in the patient’s own stem cells, there won’t be any immune response problems, and this reduces the risk of treatment.
The immune response is the major hurdle for scientists to use CRISPR in treating diseased patients.
Virus
The most accepted way of delivering CRISPR to the cells is, insert it to a non-harmful virus, which can then make its way to the cells.
But the body’s immune response will prevent the entry of viral genome to the cell, preventing CRISPR from getting into the cells.
Prof. Naldini, working to improve the precision and safety of CRISPR based medicines as a part of the project UPGRADE, suggests that changing the characteristics of the virus or delivering the CRISPR through chemical chauffeurs like nanoparticles can solve this problem. The scientists are working towards the development of such nanoparticles from lipids, sugars, and polymers.
The scientists are also trying to tackle the possibility of poor accuracy of CRISPR due to its ‘off-target’ genome editing and the chance of disrupting another gene function while inserting the new gene. The researchers are trying to improve the accuracy of CRISPR.
The Cas9 enzyme is originally found in bacterias. By gently directing that bacteria’s evolution in the lab, the team hopes to modify Cas9 so that it is more suited to act in human DNA.
A molecule called recombinase could serve the purpose of Cas9, adding genetic sequences instead of deleting them. They, too, will be evolved to match the desired genetic code.
The team expects to start the trials once the project is completed and tested.
Author: Namitha Thampi