DIY DNA synthesis for $2 a gene

UCLA scientists used DropSynth to make thousands of bacterial genes with different versions of phosphopantetheine adenylyltransferase, or PPAT. (Sriram Kosuri/UCLA)

Scientists Sriram Kosuri and Calin Plesa of the University of California in Los Angeles were frustrated by the prospect of paying up to $100 per gene from commercial vendors that sell gene sequences for scientific experiments. So they decided to invent a gene-synthesis technology that allows scientists anywhere to make their own genes quickly and efficiently.

The cost? Kosuri and Plesa estimated that their technique, called DropSynth, will cost scientists just $2 per gene. They described the technique in the journal Science.

Here’s how it works: Small sections of thousands of genes are isolated in water droplets, which are then suspended in oil. Each DNA segment gets a bar code that identifies the full gene it’s a part of, after which each segment is copied. Then DropSynth uses small beads to resort the gene fragments into the desired DNA sequences for experiments, according to a statement from UCLA.

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Usually the process of making synthetic genes either limits the size of the sequences, or it costs too much for the average lab to afford.

"This is the first time that, without a million dollars, an average lab can make 10,000 genes from scratch," Kosuri said in the statement.

Synthetic gene sequences are used for everything from screening drug candidates to understanding the role of particular genes in the body. Such experiments generally require high-throughput screening, in which thousands of cells are screened and their DNA sequenced in an attempt to understand how genes or sections of genes behave.

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To prove out their new technology, the UCLA team used DropSynth to produce bacterial genes. Each synthetic gene was as long as 669 base pairs—about triple the length of what low-cost gene-synthesis systems are able to achieve, they said.

Each gene made a different type of phosphopantetheine adenylyltransferase (PPAT), a protein essential to the survival of bacteria responsible for illnesses ranging from food poisoning to pneumonia. Because PPAT is emerging as a potential target for antibiotics, DropSynth could be useful in producing cells for drug screening, they said.

They demonstrated that concept by taking the thousands of versions of the PPAT gene they created and then adding them one-by-one to E. coli bacteria that had been engineered to lack the gene. That allowed them to see which of the synthetic PPATs contributed to the survival of E. coli.

Those surviving cells, they believe, could be used to inexpensively screen experimental antibiotics.

The UCLA scientists believe DropSynth will help scientists engineer new proteins, too. And they’re encouraging researchers around the world to try it: The instructions are posted on their website, and all the necessary chemicals are widely available, they said.