Gene editing in the human body
Safety has been proven, effectiveness is still in question
Yulia Vorobyova, Vesti
In November 2017, American scientists edited the genome in the human body for the first time in the history of medicine.
The most difficult experiment was conducted by researchers from the biotech company Sangamo Therapeutics. It was attended by 44-year-old Brian Madeux, who suffers from a severe congenital disease.
The man was diagnosed with type II mucopolysaccharidosis, or Hunter's disease. In such a disease, due to mutations, a number of enzymes responsible for the breakdown of some complex sugars and the purification mechanism are missing. As a result, "garbage" accumulates in the cells in the form of protein-carbohydrate complexes and fats, which leads to disruption of the most important organs, in particular, the heart, brain and lungs.
This ailment is quite rare, mainly men suffer from it: according to various estimates, one in 100-170 thousand people. Most patients do not even live to be 20 years old.
In the case of Made, the gene editing procedure was successful. Moreover, it was followed by three more men with Hunter's disease. The other day, specialists reported on the results of the work done and spoke in detail about the progress of the revolutionary treatment.
The lead author of the study, geneticist Joseph Muenzer, presented a report at the annual meeting of the Society for the Study of Hereditary Metabolic Diseases (SSIEM 2018).
To correct the error in the genome, scientists have developed special gene-editing enzymes – zinc finger nucleases. Similar tools were used even before the creation of CRISPR technology.
The essence of the method is as follows: patients are injected with a virus that is safe for the body, which delivers the enzyme to the right place, namely, into liver cells. The enzyme cuts a certain section of DNA and inserts a healthy copy of the gene into it (in this case, it is the IDS gene, mutations in which lead to the development of Hunter's disease).
As a result, liver cells begin to produce a vital enzyme called iduronate-2-sulfatase, which cleans up cellular "garbage". Moreover, in order for the disease to recede, it is enough that even less than 1% of all liver cells produce the necessary enzyme, experts say.
Munzer also explains that the choice fell on the zinc finger method, because it allows you to control the place of insertion of a healthy copy of the gene as accurately as possible.
Now doctors are monitoring all four men who have agreed to experimental treatment. It lasted 16 weeks. Participants received three doses of gene-editing enzymes.
In addition, they are given weekly injections of iduronate-2-sulfatase. If the body starts to produce enough of this compound on its own, the number of injections, apparently, will be reduced.
By the way, standard methods of easing the symptoms of Hunter's disease also involve the introduction of iduronate-2-sulfatase into the body, but injections should be done daily. This method can only be called maintaining a stable condition, not treatment.
Doctors clarify that during the trials of the new method, the dosage of gene-editing enzymes was different, so the condition of patients is different. So, those who received the most powerful treatment show a good improvement: the levels of harmful compounds (glycosaminoglycans) in two volunteers decreased by 36% and 63%. The other two patients with a mild form of the disease, who received minimal doses of treatment, have not yet improved.
It is important to note that no side effects were also noticed.
However, scientists admit that they cannot yet track how the production of iduronate-2-sulfatase takes place in the bodies of men. Blood tests that detect the amount of this enzyme are apparently not sensitive enough and cannot "notice" enzymes when there are very few of them, the authors of the study explain. They have already started developing a new, more sensitive test that will be useful for future work.
Colleagues of Munzer and his team note that the testing of the new method is a significant achievement in the field of gene editing and the development of new methods of genetic engineering for the treatment of specific diseases.
"This study with the addition of [new copies of] genes is an important step forward. His results are definitely of interest for [treating] a wide range of diseases," says geneticist Marianne Rots from the University of Groningen in the Netherlands.
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