San Diego’s Synthorx Adds To Genetic Alphabet, Aims for Bio-Products

Xconomy San Diego — 

[Corrected 5/7/14, 2 pm See below.] A group of scientists in San Diego who found a way to insert synthesized nucleotides into DNA—and who succeeded in coaxing the synthetic DNA to replicate in bacteria—have founded a new company to use the technology to make improved drugs and bio-products.

Their breakthrough in synthetic biology, described in research published today in the journal Nature, is expected to multiply the genetic permutations that Nature May 8, 2014enable living cells to produce proteins. Actual products based on the early-stage technology are no sure thing, of course, but San Diego-based Synthorx, says eventually it could provide important new tools for developing new, large-molecule drugs, vaccines, diagnostics, and nanomaterials.

[Clarifies and corrects the gene expression process.] DNA is made of four standard units, or nucleotides (A, C, T, and G). Strung together, the nucleotides provide instructions for the cellular machinery that builds proteins out of amino acids, with each group of three letters, or “codon,” specifying one of 20 amino acid building blocks. But a team led by Floyd Romesberg of The Scripps Research Institute has added two synthetic nucleotides, dubbed X and Y, to the DNA alphabet. Since more letters makes for more possible codons, the researchers say the technology could allow them to engineer organisms capable of incorporating a variety of synthetic amino acids—up to 152 of them—into their proteins, creating a host of proteins with new functions.

“What we’ve done is create a synthetic base pair that functions alongside natural DNA,” Romesberg said in a phone interview. The ability to insert a synthetic base pair in DNA, and to replicate the altered DNA in E. coli bacteria without changes, expands the genetic alphabet to increase the amount of information that can be stored in DNA. The research published today in Nature also shows that DNA repair systems that remove defective nucleotides from DNA will accept the synthetic X-Y nucleotides in the DNA. As a result, he said, “We have created the first organism that stores increased genetic information.”

TSRI Associate Professor of Chemistry Floyd Romesberg

Floyd Romesberg

An associate professor of chemistry, Romesberg is focused on biological and biophysical chemistry, particularly on the processes affected by the forces of evolution. He says the long-term goal of the work that began 14 years ago would apply basic principals of evolution to materials and drug development. “One could imagine making a bunch of DNA that was all slightly different, and then giving cells each one copy,” Romesberg said. “The cells then make whatever that DNA encoded.”

After demonstrating that cells can accommodate the synthetic DNA, Romesberg said the next step would be to use synthetic DNA to make amino acids that don’t exist in nature. “You have an orthogonal, clean set of new information—a new alphabet—that enables you to write new works,” he said. “We’re not there yet, but that’s the direction we’re headed.”

Romesberg was confident enough about taking that next step to found Synthorx to commercialize the technology—using the increased genetic alphabet to improve the discovery and development of new biotherapeutic drugs, diagnostics, and vaccines. One potential application is in drug screening, said Romesberg: “There is a starving need for new protein-based, therapeutic compound libraries that can be used to screen for new drugs.”

The idea is to encode E. coli (or other cells that produce therapeutic proteins) to create a much wider array of those proteins, all slightly different, than what is currently possible, giving drug … Next Page »

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2 responses to “San Diego’s Synthorx Adds To Genetic Alphabet, Aims for Bio-Products”

  1. the_caganer says:

    Amino acids are the building blocks of proteins, much like nucleotides are the building blocks of DNA. DNA -> transcription -> RNA -> translation -> Protein

    • Bruce V. BigelowBVBigelow says:

      Thanks for calling our attention to this. We’ve reworked that explanation!