"Nature" pays close attention to the fire-to-explosion CRISPR gene editing technology

Release date: 2016-03-11

Today's "Nature" has three articles discussing this technology, indicating that this technology is highly valued. In 2015, it won't win the Nobel Prize, and 2016 is still a big hit. This technology is no longer a mere technical problem, has affected the field of policy making and ethics, and has provided the entire biomedical community with a simple and economically revolutionary technology. Folk biology research has also begun to use this technology to come to the forefront. It is expected that some DIY CRISPR technology enthusiasts will soon report their research results in academic journals and conferences, and make biological academic research from the past niche to the public. Scientific research and entertainment. These are subversive concepts and changes because of the emergence of this CRISPR technology.

Professor Timothy Doran, a molecular biologist at the Commonwealth Scientific and Industrial Research Organisation (CSIRO), is 11-year-old daughter who is allergic to eggs. About 2% of children worldwide are allergic to eggs. These patients cannot be vaccinated with eggs. Doran, a professor of biology, envisions using the powerful gene editing tool CRISPR–Cas9 to solve this problem.

Most egg allergens are four proteins in the protein. Doran's colleagues used bacteria to encode one of the mutated proteins, which no longer reacts with the serum of egg allergy patients, suggesting that these protein structures are modified completely. It is possible to let eggs allergic patients eat eggs and inoculate vaccines made from chicken embryos. The overall idea is to modify these four protein genes in chickens with CRISPR, which can produce eggs without allergens.

The Doran team hopes to come up with the first generation of genetically modified chickens in 2016 to prove the conceptual feasibility of this idea. Doran knew that the chicken with the modified gene had to be authorized by the regulatory authorities, but he hoped that the daughter would have a chance to benefit from it.

Limited by labor and efficiency, scientists have only genetically modified a handful of carefully selected species. The technology of Cisco has revolutionized this limitation because it is not only efficient but also simple. The chicken is just a member of the CRISPR Zoo. In the past two years alone, genetically modified animals such as monkeys, mammoths, mosquitoes, and pet pigs have become headlines in science. Scientists have used this technology for agriculture, drug production, and resurrection of extinct organisms. This is not only a revolution in technology, but also a transformation of the scientific paradigm. Bruce Whitelaw, an animal biotechnology expert at the Roslin Institute in Edinburgh, UK, said that many ideas in the past did not dare to think about it, and the entire biomedical community turned its attention to the field of genetic editing.

Given that these new species may affect ecosystems, regulators around the world have not yet had an ideal response to these new organisms, especially those that can be used as food or released into the wild. The head of the US think tank is concerned about this, saying that this simple and cost-effective gene editing technology may bring uncertain risks and it is difficult to avoid certain people making harmful species. Eleonore Pauwels, a biotechnology regulatory policy expert in Washington, said that the use of CRISPR animals has prompted scientists and policy makers to openly talk, and she hopes that such discussions will help determine which types of CRISPR can benefit humans, other species and science, and must limit this. Abuse of technology.

Increasing disease resistance The most recognizable application of CRISPR in agriculture, scientists have improved the animal's disease resistance by modifying animal genes, thereby reducing drug use. San Francisco biotech business owner Brian Gillis hopes to use genetic modification technology to transform bees to avoid the massive death of bees caused by disease and parasitic infections.

Gillis is working on the genome of the “healthy bee”, which obsessively cleans the hive and removes larvae from sick and infected bees. Hives with these bees are not vulnerable to pathogens such as cockroaches and fungi. If you can identify the genes that produce these behaviors, you can transfer the genes to other bee populations and improve their disease resistance.

BartJan Fernhou, chairman of the Boxmeer Bee Research Group, is a scholar who studies the ability of bees to fight cockroaches. He believes that this strategy is difficult to achieve because the specific genes for such behavior are not found, and the root causes of these behaviors are more complicated. Even with this gene, the goal can be achieved with traditional breeding techniques, and there is no need to adopt this high-risk transgenic strategy.

Despite this concern, it seems that there is no impact on the speed of research on transgenic disease resistance. The Rosslyn Whitelaw Institute and other teams have used CRISPR technology to transfer pigs to antiviral genes, a technology that is expected to bring lucrative profits to the pig industry. The Whitelaw Institute is also using other gene editing techniques to modify immune-related genes and improve the ability of domestic pigs to fight African swine fever.

Randall Prather of the University of Missouri in Colombia has mutated a cell surface protein in pigs, making the pig less susceptible to a serious lethal respiratory virus. There are also scientists using similar strategies to transform cattle to improve the ability to resist tomystry infections to prevent sleeping sickness.

The Whitelaw Institute hopes that regulators and consumers will be more optimistic about these genetically modified animals. Some governments are also considering whether it is necessary to treat CRISPR technology by means of managing genetically modified technologies. The latter has not been transferred to other genes, but has only modified the genes of the species itself.

Doran's plan is to transform allergenic proteins, which must be controlled to a certain extent and must avoid affecting the embryonic development of the chicken. This is the hallmark of CRISPR technology, which allows precise editing of target gene sequences. CSIRO molecular biologist Mark Tizard said that CRISPR has become the saviour of the savior who accurately destroys allergens.

The general procedure for the use of CRISPR in mammals is to induce the production of eggs with drugs, to remove the eggs for editing, and to be transplanted to the uterus after fertilization. There is still a problem with the use of CRISPR for birds. The fertilized egg is tightly bound to the egg yolk, and the removal of the fertilized egg destroys the embryo. Chicken eggs that are not fertilized are difficult to remove, and CRISPR cannot be injected directly into chicken eggs. Once the eggs are produced, the development process has begun and it is very difficult to perform precise genetic editing.

Tizard and Doran are preparing to start with primordial germ cells (PGCs), which can turn into sperm or eggs. Chicken PGCs can enter the bloodstream during development, giving scientists a simple way to collect chicken PGCs. These cells are genetically edited indoors and then matured. The CSIRO team has developed a technique for editing CRISPR elements directly into the blood to edit PGCs.

Scientists also plan to use the CRISPR technology to transform the entire genome of chickens. The chicken has a special name, CRISPi chicken, which can be used to simply mass-produce the protein of interest. Regulators have also recognized this drug manufacturing method. In 2006, the EU authorized the use of goat milk to make an anticoagulant protein. In 2009, it was also authorized by the US FDA. In 2015, the European Union and the US FDA authorized the marketing of anticholesterol drugs made from genetically modified eggs.

The plan sounds crazy, but efforts to get elephants closer to mammoths have been going on. Last year, the University of Chicago geneticist Vincent Lynch found that there is a genetic version of mammoth cells responsible for low temperature tolerance and growth of hair. Mice with similar gene versions also improve cold tolerance. Church said he has edited 14 similar genes in elephant embryos. However, it is not so simple to edit, fert and raise low temperature resistant mammoths. It is not ethical to transplant this embryo to endangered elephants. Their laboratory is planning to make artificial uterus for full artificial cultivation.

There are also some technologies that want to resurrect extinct species, and Ben Novak of the University of California, Santa Cruz, hopes to resurrect a pigeon. This pigeon, which was ubiquitous at the end of the 19th century, was extinct because of human over-hunting. His team is currently using the specimen specimen pigeon DNA for sequence alignment with existing pigeons. It is planned to use the PGC cell method similar to the Doran group to genetically modify other pigeons to make these pigeons closer to the extinct pigeon.

Novak said that the current technology is not able to modify the ability of hundreds of genes to be modified simultaneously. But CRISPR gave them the best choice, hoping to realize his dream of being alive and dead.

In addition, the use of CRISPR for birth control to eliminate extinct mosquitoes, to improve the growth rate of fish and the application of low temperature resistance, genetic modification to minimize the pet animals, the use of this technology to create a variety of disease models and other applications, respectively Some scholars have done it. In short, the number of animals and plants that use CRISPR technology to transform genes is increasing, and the rate of increase is getting faster and faster.

Source: Science Network

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