Let the cells "do not invade" - the human genome writing plan turns to design "super safe" cells

Let the cells "do not invade" - the human genome writing plan turns to design "super safe" cells

May 03, 2018 Source: Science and Technology Daily

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The Human Genome Project is designed to target human cells against a variety of viruses, including HIV.

The figure shows that the virus infects a cell line. Image source: "Nature" magazine official website

On June 2, 2016, Jeff Boyko of New York University, George Church of Harvard University, and Pharim Isaac, a biologist at Yale University, published in the journal Science. It is announced that it will raise $100 million to launch the 10-year Human Genome Project (GP-write) and synthesize the human genome from the ground up.

Once the news was released, it triggered a strong concern among the scientific community and the public about the “synthesis” of humans in the laboratory. But after two years of turmoil and turmoil, the project's leadership team announced in Boston on May 1 that it would temporarily abandon its attempt to create a human genome from scratch, focusing on editing cells to fight viral infections.

So why do they so so favor the so-called "ultra-safe" anti-viral cells? What are the difficulties in implementing the new plan? Both Science and the British magazine Nature have paid attention to the report on the 1st.

"ultra-safe" cells

The researchers said that the main idea of ​​the latest project is clear: to redesign the cellular genome of humans and other species to make cells "super safe."

Nature reported that researchers say that "super-safe" cells will benefit multiple areas. For example, when a drug company uses cells to make therapeutic proteins, if the cells are infected with a virus, the entire production must stop; and the antiviral human cell line allows the company to be free of virus contamination when making vaccines, antibodies, and other biopharmaceuticals. risk.

Moreover, drug-resistant cell lines are also safer and more effective pharmaceutical plants, and do not require much monitoring. In addition, these cells can also help scientists create protein drugs that have chemical "garments" similar to those found in human proteins, thereby reducing the risk of rejection of the body's immune system.

Farin Isaac, a member of the Human Genome Writing Program Science Executive Board, said that, more importantly, new projects may help researchers go beyond current editing tools such as CRISPR to get broader, better genome redesign tools. . He envisions that in the future scientists will "rewrite the genome to give the organism a whole new function" - such as the ability to breed only in a tightly controlled environment in the laboratory.

In addition to being able to fight the virus, organizers are also considering other ultra-safe cell characteristics, such as fighting cancer mutations, radiation, and freezing.

Virus protection against genetic code

So, how to make the cells "a hundred poisons do not invade"?

The researchers explained that making cells immune to viruses requires "recoding," which is the change in the DNA sequence of a cell, a so-called codon that decodes the amino acid composition of a protein.

Since multiple codons can represent the same amino acid, researchers can swap out redundant codons and retain important cellular functions. By eliminating certain codons, they can safely remove some cellular mechanisms that translate these codons into proteins. When a virus "hijacks" a cell and attempts to replicate it, it also relies on these cellular mechanisms to decode its own genes.

The chromosome biologist Toston Waldminghos of the University of Marburg in Germany did not participate in the genome preparation project. He said that because the re-encoded cells "basically speak another language", they cannot "entertain" the virus and become resistant to the virus. According to a statement issued by the Human Genome Project Planning Group on the 1st, in order for human cells to resist the virus, there must be at least 400,000 changes in the genome.

New projects may require the technology that the founders and leaders of the Human Genome Project have developed in the lab. In 2005, Isaac began experimenting with recoding the genome of E. coli. In a 2013 paper, Isaac, Qiu Qi and collaborators exchanged 321 codons in E. coli to make them resistant to certain viruses. Currently, two laboratories are working to remove other codons from E. coli.

In response to the idea of ​​cell recoding, Waldminhos said: "It works in E. coli, and I hope it can also work in human cells. This is not a new scientific insight... but I still think this is worth it."

The actual problem still exists

The new project is ideally full, but the reality is very skinny. There are still many challenges to achieving this project. The first problem is the funding problem. Although at the 1st meeting, a gene editing technology company expressed its willingness to contribute its own technology, people or groups willing to take out real money are still missing.

In addition, it is unclear how the project will be implemented. Boyko hopes to prioritize the recoding of human and mouse genomes. He said that if the new project is modeled on the ongoing yeast genome project (Sc2.0), then the participating groups will be funded.

The Human Genome Project has about 200 scientists involved, some of which have spontaneously formed nine “working groups” to deal with a variety of topics, from the development of technology and infrastructure to the ethical, legal and social impact of the project, and for the future. Work to develop a “charter” and a “road map”.

Finally, intellectual property issues may also complicate new projects. Bojko said: "In synthetic biology and synthetic genomics, there is usually only partial intellectual property."

Isaac also pointed out that Harvard University, Yale University and Massachusetts Institute of Technology all have patents related to recoding. However, there is an intellectual property team in the Human Genome Writing Program Working Group that will explore how the technologies used in the program and possible future breakthroughs can be shared.

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