Author: Tierna Date: 2018-05-15
Retinitis pigmentosa is an inherited disease that affects the retina and its functional degradation. It is a difficult disease in ophthalmology, also known as incurable disease. In recent years, with the continuous improvement of gene editing technology, scientists have finally made new breakthroughs in the latest research: they use CRISPR technology to restore the retinal function of mice with retinitis pigmentosa, a major advancement or Open a new direction for the treatment of the disease.
Image source: allaboutvision
The results of the study were published in the American Journal of Ophthalmology "Ophthalmology" on May 10. This is also the first time researchers have successfully applied CRISPR technology to dominant genetic diseases. At the same time, this tool may play a role in hundreds of diseases including Huntington's disease, Marfan syndrome and corneal dystrophy.
DOI: https://doi.org/10.1016/j.ophtha.2018.04.001
1. "Terror" retinitis pigmentosa
Retinitis pigmentosa is a rare group of hereditary diseases caused by one of more than 70 genes. It involves the breakdown and loss of cells in the retina (photosensitive tissue at the back of the eye). The disease usually occurs in childhood and progresses slowly, affecting peripheral vision and night vision. Most people lose most of their vision in early adulthood, and legal blindness occurs after the age of 40, and there is currently no cure. It is estimated that about one in four thousand people worldwide are affected by the disease.
The author of the paper, Dr. Stephen H. Tsang, and his colleagues tried to create a more flexible CRISPR tool so that more patients could be treated without being limited by their individual genetic characteristics. Dr. Tsang called the technique genome surgery because it removes bad genes and replaces them with normal functional genes.
Image source: Kelly Irvine/NIST
2 , CRISPR technology brings new ideas for retinitis pigmentosa
Since 2012, CRISPR gene editing technology has been applied in a variety of fields, which has completely changed the speed and scope of scientists to modify living cell DNA. However, even if the genomic surgery is extraordinary, there are still some shortcomings in CRISPR that need to be overcome.
Diseases such as autosomal dominant retinitis pigmentosa present a special challenge for researchers: in autosomal dominant genetic diseases, patients inherit only a mutant copy and a pair of autosomes from their parents. A normal gene. Therefore, for scientists who hold CRISPR, their challenge is to edit only the mutant gene without changing the healthy gene.
In contrast, humans with autosomal recessive diseases inherit two copies of the mutated gene. When two copies of a gene are mutated, a method of directly replacing the defective gene is involved (currently, six pharmaceutical companies are studying gene therapy for recessive retinitis pigmentosa, but no one has developed a dominant Status of treatment)). Dr. Tsang and his colleagues were inspired to propose a better strategy for treating autosomal dominant diseases: it allowed the removal of old genes and replaced them with a good gene without affecting their normal function.
This so-called "ablate-and-replace" strategy can be used to develop a CRISPR toolset for all types of mutations that reside in the same gene (rather than a certain type of mutation), especially Multiple types of mutations result in the same condition. For example, any of the 150 mutations in the rhodopsin gene may cause retinitis pigmentosa. Because Dr. Tsang's technology can be applied in a mutation-independent manner, it represents a faster, more economical strategy for treating dysplastic diseases with genomic surgery.
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3 , the principle of treatment
Often, CRISPR researchers design a short code sequence called a guide RNA to match the part they want to replace. They attached the guide RNA to a protein called Cas9 and then roamed together in the nucleus until the target DNA was found.
Next, Cas9 melts the DNA and pushes it into the guide RNA. Then, using the cell's natural gene repair mechanism, cut out the error code and induce the cell to accept the correct code. It is worth mentioning that Tsang designed two guide RNAs to treat autosomal dominant retinitis pigmentosa caused by rhodopsin gene mutations (rhodopsin is an important therapeutic target, and its mutation leads to about 30% Autosomal dominant retinitis pigmentosa and 15% hereditary retinal dystrophy).
4 , the advantages of CRISPR
This technique allows for a greater degree of deletion of the genetic code that permanently destroys the target gene. Dr. Tsang found that using two guide RNAs (rather than a guide RNA) increased the chances of cleaning bad genes from 30% to 90%. In the study, they combined this genomic surgical tool with gene replacement technology to introduce healthy genes into the retina using adeno-associated viruses.
Another advantage is that this technique can be used for non-dividing cells, which means it can focus gene therapy on non-dividing adult cells (such as cells of the eye, brain or heart). To date, the use of CRISPR in dividing cells has been more effective than non-dividing cells.
5 , the prospects are considerable
Tsang used an objective visual test to assess retinal function in mice after treatment, and the results showed significant improvement. Previous studies of CR on retinal disease relied on a less objective measurement method (including assessing the frequency of the mouse turning the head toward the light source), and now Tsang is confirmed with a new electroretinography, with untreated mice. Retinal degeneration after treatment is slowed down compared to eyes.
Tsang expects that human trials will be conducted in three years. "Genome surgery is coming, and ophthalmology will be the first area to see this surgery." He is so sure.
References: 1) CRISPR for Eye Disease Moves Closer to Reality
Source: Bio-Exploration
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