2017, four surprises for genetic editing

Release date: 2017-12-29

In 1953, scientists Watson and Crick discovered the DNA double helix structure. Since then, people have known that genetic information is composed and expressed by genes. In 1963, a decade after the theory of gene double helix was proposed, a new generation of scientists formally proposed gene editing therapy—by knocking out or replacing a part of the gene, changing the expression of the gene, increasing or decreasing certain cellular functions to treat and cure. Certain diseases.

Looking back on 2017, the gene editor brought us a lot of surprises.

The first human genetic editing surgery in the United States

In January 2017, the University of California, San Francisco Children's Hospital first attempted to perform gene editing directly in the human body. Scientists injected a gene editing tool into the blood of a 44-year-old patient to treat Hunter's syndrome by permanently altering the gene. Hunter's syndrome is a rare, life-threatening genetic disease caused by genetic mutations. The patient's cellular metabolic waste cannot be decomposed, accumulates in tissues and organs, and eventually produces dysfunction.

The gene editing tool used by this scientist is the first generation of gene editing tool, zinc finger nuclease technology. The sequence of positioning of this technology is longer and the operation is relatively complicated, but the accuracy of gene editing is relatively higher. Success, gene editing therapy or will enter a new stage of development.

The first human embryonic CRISPR gene editing experiment in the United States

In August 2017, American scientists used CRISPR technology to remove the MYBPC3 gene that causes hypertrophic cardiomyopathy from a human cell stage embryo, again demonstrating the strong genetic editing capabilities of CRISPR.

This is the first genetic editing experiment in human embryos in the United States. It is currently only performed in laboratories. More than 10,000 human diseases are caused by a single genetic abnormality. If you use CRISPR technology to correct it during the embryonic period, it will cure a series of genetic diseases. Save millions of lives.

In this experiment, the researchers used human eggs from 12 female donors and a male sperm carrying the MYBPC3 gene to construct human embryos. Then, when the sperm is injected into the egg, CRISPR plays a role in cutting off the defective gene. With the division and growth of embryos, many cells self-repair using the corresponding normal genes in the maternal genome, correcting the original defective genes. In the experiment, 72% of the cells appeared to be corrected, and the researchers did not observe any off-target effects.

Shoukhrat Mitalipov, a lead author from the Oregon Health and Science University, said that in fact, the researchers did not edit or modify any genes, and only used CRISPR technology to correct the mutant genes. In the future, this technology has the potential to greatly reduce the burden on families carrying this genetic disease.

Alta Charo, a bioethicist at the University of Wisconsin-Madison, believes that the Institute demonstrates the potential of CRISPR to treat genetic diseases beyond the concerns raised by the technology. This research has taken an important and inspiring step in the study of how to safely and accurately edit embryonic genes.

Gene editing is expected to safely transplant pig organs to human patients

Also in August, scientists used gene editing technology to remove dangerous viruses from DNA in pigs, which is expected to produce human transplantable organs on pigs.

The porcine endogenous retrovirus is permanently embedded in the porcine gene. Recent studies have shown that this virus can infect human cells and pose a potential threat. The existence of this virus has always been a major obstacle to the growth and development of transgenic pigs. And prevent transgenic pigs from providing kidneys and other transplant organs to human patients.

In the study, the researchers used a variety of gene editing to clone the primary porcine fibroblasts to eradicate endogenous retroviruses and successfully bred virus-inactivated pigs, thus laying a foundation for providing safer and more effective xenotransplantation. Good foundation.

CRISPR gene editing accuracy has been greatly improved

The CRISPR-Cas9 technology reliably detects and cleaves target DNA sequence fragments, but repairing this cut as desired is a tricky process, up to 50% when the goal is to correct base changes in DNA that cause genetic disease. The error rate is a problem that cannot be ignored.

In November of this year, a research team led by Krishanu Saha, a professor of biomedical engineering at the University of Wisconsin-Madison, developed a new method that would make this repair less error-prone.

Compared to standard CRISPR technology, this new method increases the probability of accurately rewriting DNA sequences by a factor of 10. These researchers assemble a complete molecule using a molecular glue called an RNA aptamer. The CRISPR Repair Kit delivers this kit to DNA cleavage sites for greater repair accuracy.

For example, in the addition of fluorescent labels, this method allows researchers to easily identify all precisely edited DNA sequences in a cell population. “By looking for these fluorescent labels, we are able to achieve 98% accuracy,” Saha said.

At the same time, the new method has several other advantages compared to the prior art. First, the kit contains only non-viral reagents, which simplifies the production process and reduces the safety issues associated with future clinical applications of genetic surgery. Second, adding an RNA aptamer to this kit is easier than modifying the Cas9 protein and provides greater flexibility.

Although there have been many amazing advances in the field of gene editing in 2017, it is not to be overlooked that due to its current technical, legal, and ethical issues, genetic editing is generally in the field of clinical treatment. Still progressing slowly, currently, it is mainly concentrated in diseases caused by single gene mutations and rare diseases such as beta thalassemia and sickle cell disease.

According to foreign media reports, a company named "CRISPR" in the United States is also the first company to obtain permission from European regulators. It will conduct clinical trials next year, which will use CRISPR technology to solve the genetic defects of patients with beta thalassemia. The company also plans to apply to the US Food and Drug Administration (FDA) for approval of clinical trials for the treatment of sickle cell disease in the first half of next year.

In Europe, about 15,000 people suffer from beta thalassemia, and about 100,000 people in the United States suffer from sickle cell disease, both of which are genetic diseases caused by genetic mutations that cause hemoglobin (one in red blood cells). An important protein) does not normally carry oxygen throughout the body. Normally, both parents carry an abnormal gene, and the child will develop the disease.

At the same time, researchers at Stanford University School of Medicine will also use CRISPR to treat sickle cell disease for clinical trials. The research team is led by pediatric associate professor Matthew Porteus and plans to conduct clinical trials between 2018 and 2019.

Researchers at CRISPR Therapeutics and Stanford University School of Medicine have taken different approaches to the study of sickle cell disease.

Both groups extracted stem cells from the patient's bone marrow and then changed them using CRISPR technology, but instead of trying to repair sickle cell-deficient genes, CRISPR Therapeutics used editing tools to make cells produce another protein, an infant-type Hemoglobin, the modified cells will be reinfused into the patient, and the company is using the same method to treat patients with beta thalassemia in Europe.

In Stanford's sickle cell research, researchers will attempt to directly correct hemoglobin gene mutations and convert sickle cells into normal cells, and Stanford University will conduct experiments at the Curative and Definitive Medicine Medical Center.

Compared with traditional treatment methods, genetic bio-editing technology will bring more possible cures to patients and reduce the burden of family treatment.

For example, at this stage, normative lifelong blood transfusion and de-iron therapy are the main treatments for severe beta thalassemia, but the cost of treatment is extremely high, and frequent lifelong treatment is needed. According to the "Chinese Thalassemia Blue Book", the traditional lifelong Blood transfusion and iron treatment costs about 4.8 million yuan in a lifetime, which is a heavy burden that most families cannot afford.

In addition, thalassemia hematopoietic stem cell transplantation is also a widely practiced clinical cure for thalassemia, but according to the "Chinese Thalassemia Blue Book", in 2016, the number of people looking for transplant donors to the Southern Hospital was 2,255. 78 cases of thalassemia transplant calculations are completed each year, and the longest stay period is nearly 30 years.

Gene therapy biotechnology often has the advantages of no need to match, reduce the complications of transplantation, and does not need long-term use of immunosuppressive drugs, and even achieve the goal of radical cure.

Source: Medical Valley

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