Let the cells "poisonously invade"

On June 2, 2016, scientists led by Jeff Boyko of the University of New York, George Kirch of Harvard University, and biological engineer Faren Isaac of Yale University published articles in the journal Science in the United States. It announced that it will raise 100 million U.S. dollars and launch the 10-year Human Genome Project (GP-write) program to synthesize the human genome from the ground up in the laboratory.

As soon as the news was released, it provoked scientific and public concerns about the laboratory's "synthesis" of human beings. But after two years of turmoil and turmoil, the project's leading group announced in Boston on May 1 that it will temporarily forgo its attempt to create the human genome from scratch, focusing on editing cells to fight viral infections.

So why do they so favor the so-called "ultra-safe" antiviral cells? The difficulties faced by the implementation of the new plan? "Science" and the British "Nature" magazine are concerned about in the 1st report.

"Ultra safe" cells

The researchers said that the main thrust of the latest project is clear: Redesign the cellular genomes of humans and other species to make cells "super safe."

"Nature" magazine reported that researchers said that "ultra-safe" cells will benefit many fields. For example, when a drug company uses cells to make therapeutic proteins, if the cells are infected with the virus, the entire production must stop; and the anti-viral human cell lines allow companies to manufacture vaccines, antibodies, and other biological drugs without virus contamination. risk.

Moreover, drug-resistant cell lines are a safer and more effective medical facility and do not require much monitoring. In addition, these cells can also help scientists make protein drugs that resemble the chemical “frills” that appear in human proteins, thereby reducing the risk of rejection of the body's immune system.

Dr. Faren Isaac, member of the Scientific Executive Board of the Human Genome Writing Program, said that, more importantly, the new project may help researchers move beyond current CRISPR editing tools to get broader and better genome redesign tools. . He envisions that in the future scientists will "rewrite the genome so that the organism has a new function" - such as the ability to reproduce only in the laboratory under strict control of the environment.

In addition to being resistant to viruses, organizers are also considering other ultra-safe cell features such as fighting cancer mutations, radiation, and freezing.

Virus protection of genetic code

So, how do you make cells "poisonous and non-invasive"?

The researchers explained that making cells free from viruses requires "recoding", which is to change the DNA sequence of the cells, the so-called codons, which can decode the amino acid composition of proteins.

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

Toston Waldminthus, a chromosomal biologist at the University of Marburg, Germany, did not participate in the genome preparation program. He said that because the recoded cells "essentially speak another language", they cannot "host" the virus and they are resistant to the virus. According to a statement issued by the leading group on the preparation of the human genome plan, on the 1st, to make human cells resistant to viruses, 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 Writing Program have spawned in the lab. In 2005, Isaac began experiments to recode the genome of E. coli. In a 2013 paper, Isaac, Qiu Qi, and co-workers exchanged 321 of one codon in E. coli, making it resistant to certain viruses. Currently, two laboratories are working hard to remove other codons of E. coli.

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

The actual problem still exists

The new project is full of ideals, but the reality is very skinny. To realize this project, there are still many difficulties. First and foremost is the funding issue. Although at the 1st meeting, a gene editing technology company expressed its willingness to contribute its own technology, people or groups willing to show real money were still missing.

In addition, it is not clear how the project will be implemented. Boyko hopes to give priority to 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 group that chooses to participate will provide funding.

About 200 scientists are involved in the preparation of the Human Genome Project, and some of them have spontaneously formed 9 “workgroups” to deal with various topics ranging from the development of technology and infrastructure to the moral, legal and social impact of the project, and for the future. Work to establish "constitution" and "road map."

Finally, intellectual property issues may also make new projects more complex. Boyko said: "In synthetic biology and synthetic genomics, usually only part of the intellectual property rights."

Isaac also pointed out that Harvard, Yale and MIT all have patents related to recoding. However, there is an intellectual property team in the Working Group for the Human Genome Project, which will discuss the technologies used in the program and how future breakthroughs may be shared. (Reporter Liu Xia)


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