"Rewriting" yeast genomes: Paving the way to create human DNA from scratch

20170801100000, Zayani Bhatt
"Rewriting" yeast genomes: Paving the way to create human DNA from scratch
Does the chance to solve some of the world’s biggest human health challenges, also give scientists the chance to play ‘God’?
Jeff Boeke, director of the Institute for Systems Genetic s at New York University School of Medicine, has been working with his team on "rewriting" the yeast genome or, creating new yeast DNA codes to be transcripted into yeast cells.

The controversial project aims to supplement Genome Project-write or GP-write, which focuses on creating new genomes for humans and other animals that began in June 2016 by Boeke, and a group of other scientists, including the controversial geneticist from Harvard University, George Church.

The concept is that synthetic human genomes created, can be inserted into ordinary human cells whose natural DNA has been removed. This should, theoretically, then allow the scientists to match genetic sequences to their relevant traits, disease processes, and physiological functions.

A secret initial meeting to discuss GP-write was conducted in May this year and many experts are concerned about the ethical, legal and social issues, as well as skeptical as to whether the team will be able to fully synthesise human DNA.

Synthetic sequences are laboriously created from scratch


Now, Boeke and his team have separately begun to “rewrite” the yeast genome or, creating new yeast DNA codes to be put into yeast cells.

The team hopes that this would be a stepping stone for GP-write and reveal basic, hidden rules that govern the structure and functioning of genomes and also possibly reveal new and useful characteristics that can yield new vaccines, biofuels or be part of the drug-manufacturing process in pharmaceutical factories.

"[Cell lines] have been cultured in dishes in labs for decades. But you can't engineer the genomes — the tools for doing that are quite crude, relatively speaking," he says. A synthetic cell that lacked unnecessary genetic material could, consistently produce useful drugs to treat disease.

To design a stretch of DNA, the team begins with a stretch of normal, nature-made DNA and uploads that sequence onto a computer. Then, through an internally designed algorithm, specific changes are made to the sequence.

This altered sequence then becomes a blueprint and is sent to a company that manufactures chunks of the DNA containing the sequence. Finally, back in the laboratory, these short strands are joined together to make long sections of DNA.

Boeke's research has so far built one-third of the yeast genome and he hopes the rest will be constructed by the end of the year. But it will take longer to test the new DNA and fix problems, and subsequently combine the various chunks to complete the synthetic genome, he says.

Rewriting DNA, not a new concept


Rewriting DNA is not a new concept and has already been tested in some viruses and bacteria. Australian scientists recently announced that they had created a new genome for the Zika virus so they can better understand it and therefore develop medication.

At Harvard University, researchers Jeffery Way and Pamela Silver are developing harmless strains of salmonella DNA to be used as a vaccine against food poisoning that is caused by Salmonella, E. coli and Shigella.

To render the bacteria harmless when picking up DNA from other bacteria, requires altering the genome in 30,000 sites.

“The only practical way to do that,” Way says, “is to synthesize it from scratch.”

Experts still uncertain about synthesising DNA from scratch


But many experts are still uncertain about Boeke's project or GP-write. Drew Endy, a biologist at Stanford and bioethicist Laura Zoloth of Northwestern University, are two such individuals.

Whilst they said they were “heartened to see” that the leaders of GP-write have started discussions of ethical, legal and social issues, the idea of making a human genome is still a sensitive one.

Attorney Nancy J. Kelley, who organised the secret meeting in May and helped found the New York Genome Center, also mentioned that ethical concerns were only given a passing mention.

“You can only introduce the concepts. You can’t really discuss them or raise a debate about them in the paper," she added.

Zoloth and Endy were against the pursuit of the synthesis of human DNA, but the project has already begun taking shape with support from the Centre of Excellence for Engineering Biology, which will oversee the project and California-based software company Autodesk, which has committed USD250,000.

But more work still has to be done to convince the scientific community and the team recognises that.

“The notion that we could actually write a human genome is simultaneously thrilling to some and not so thrilling to others,” Boeke said. “So we recognize this is going to take a lot of discussion.” MIMS

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Sources:
https://www.statnews.com/2016/06/02/project-human-genome-synthesis/
https://www.statnews.com/2017/07/26/scientists-build-dna-scratch-alter-lifes-blueprint/
http://www.cnbc.com/2017/05/02/synthetic-dna-scientist-says-it-could-be-inside-humans-within-5-years.html