Its birth in 2016 was greeted with near hysteria over “secret meetings” and dire warnings about hubristic scientists creating made-from-scratch human genomes and designer babies. Its first birthday was overshadowed by the little matter of falling $99.75 million short of the $100 million fundraising goal it had very publicly set.
But two years in, an ambitious project to synthesize genomes — including human ones — is moving on from its shaky start and plunging in to the practical work of creating better genomes than nature did. As some 200 scientists participating in “Genome Project-write” met in Boston on Tuesday, the group announced its first target: creating cells that could never be infected by viruses, and that perhaps would also be resistant to other killers.
“There is very strong reason to believe that we can produce cells that would be completely resistant to all known viruses,” said Jef Boeke, director of the Institute for Systems Genetics at NYU Langone Medical Center and one of the four leaders of GP-write. “It should also be possible to engineer other traits, including resistance to prions and cancer.”
The genome writers also scored their biggest corporate partnership yet. Paris-based Cellectis announced on Tuesday that it was providing its genome-editing tools, TALENs, to GP-write co-leader George Church of Harvard for his lab’s part of the project, creating virus- and prion-resistant human cells. Such cells, Cellectis CEO Andre Choulika told STAT, “can be used to make universal CAR-T cells,” cancer-killing immune cells that need not come from the patient, as today’s CAR-T therapies do, but from healthy donors.
GP-write builds on the original Human Genome Project, which “read” the 3 billion molecular letters of humankind’s genetic blueprint. After all the speculation over what GP-write would actually do, Boeke said, “it’s nice to have a concrete goal.” If the goal is realized by the dozens of labs that are expected to work on the project (and to raise their own funding), the ultra-safe human cells could do for stem cell treatments — regenerative medicine — what pasteurization did for milk.
Resistance to viruses and more would be accomplished by a process called recoding, which depends on the fact that the genetic code — which sequences of DNA letters “spell” which amino acids — is redundant. Each three-letter string of DNA letters, called a codon, codes for the production of a particular amino acid. CAG codes for glutamine, for instance, AAA for lysine, and TGG for tryptophan. Hundreds or thousands of amino acids are linked together to form proteins such as insulin, collagen, dystrophin, myosin, and the thousands of others needed for life.
There are only 20 amino acids (and a “stop” signal) but 64 combinations of the four DNA nucleotides. And life can get by with only one codon for each amino acid. Recoding means choosing the GTT triplet for, say, valine, and wherever any of the three redundant ones (GTC, GTA, and GTG) appears in the genome, replacing it with GTT.
“Recoding means that every instance of one codon is replaced by another, effectively erasing one codon from the ‘genetic code’ table,” Boeke said.