Gene therapy of glaucoma
The CRISPR gene editing method made it possible to cure mice from glaucoma
Marina Astvatsaturyan, Echo of Moscow
Researchers from The University of Iowa applied the CRISPR/Cas9 system to correct the genetic mutation that causes glaucoma in live mice, as well as in the culture of cells of the retinal tissue of the eye called the trabecular network.
Article by Jain et al. CRISPR-Cas9–based treatment of mycilin-associated glaucoma is published in the journal Proceedings of the National Academy of Sciences.
A group led by Val Sheffield edited a gene that encodes the protein myocilin. A mutation in this gene leads to the accumulation of myocilin in cells, which indirectly, through stress in a certain intracellular structure called the endoplasmic network, causes an increase in intraocular pressure and, as a consequence, the development of two types of glaucoma.
According to the researchers, editing this mutation by the CRISPR system led to a decrease in intraocular pressure in model mice with glaucoma.
"This study demonstrates the potential of CRISPR-mediated genomic editing of glaucoma associated with a myocilin mutation in humans, as well as the possibility of eliminating the consequences of other mutations that cause certain diseases associated with undesirable accumulation of the gene product," the Genome Web portal quotes the authors (CRISPR Editing in Mice Disrupts Glaucoma-Causing Gene Mutation).
Sheffield and colleagues created cell lines of eye tissue, one of which did not carry a mutation for myocilin, and the other was with the most common version of the mutation that causes glaucoma in adults. As expected, in the second case, the activity level of the mutant myocilin gene associated with endoplasmic network stress was significantly increased.
The authors also created a special adenovirus to deliver the entire editing apparatus into the cells by the CRISPR system. In particular, they designed an RNA-conductor molecule that targets the part of the myocilin gene where it is possible to suspend the reading of information from this gene and the subsequent production of the myocilin protein.
After introducing such an adenovirus complex into a cell line with a mutant myocilin gene, scientists observed a decrease in protein levels compared to the control line.
The adenovirus carrier of the CRISPR system was also introduced directly into the eyes of mice with a glaucoma model. When the procedure was performed on young mice who were less than a month old and had not yet begun to develop increased intraocular pressure, it turned out that gene editing could completely prevent the disease. Mice older than nine months reacted differently to editing: their intraocular pressure decreased.
In a tissue culture from human trabecular network cells, CRISPR editing reduced the activity of the mutant gene and reduced the release of the myocilin protein into the medium, which indicates a correction of the mutation.
Portal "Eternal youth" http://vechnayamolodost.ru