Before synthetic biology can retool the economy, save the planet, or help put people on Mars, it’s going to have to become significantly easier to use.
Take computers. If you wanted to do anything useful with a computer in 1965 and you weren’t a computer scientist, you were out of luck. There were no app stores, websites, or word processors. Not even a mouse. Using a computer in those early days meant getting your hands dirty. You had to know how to program, and you might even need to solder. In essence, you had to become an expert.
Like it or not, synthetic biology is in the same boat today.
Say you want to make an enzyme. If you aren’t trained in molecular biology and don’t possess a plethora of laboratory equipment, you’re basically out of luck. Manufacturing an enzyme the traditional way requires a laundry list of technical feats: DNA synthesis and molecular cloning. Genetically manipulating and growing living cells. And, in most cases, target molecules must also be extracted and purified before they can be studied or used. A trained expert might be able to do all of this in a week.
Synthetic biology — at least as it is traditionally practiced — is not meant for the uninitiated, or for the faint of heart.
Making proteins before lunch
Arbor Biosciences is working to change that by making many of the traditional methods obsolete. In 2016, they launched their myTXTL® Cell-Free Expression product line which allows rapid and high-yield protein production from a DNA template in a simple cell-free system. Using a master mix containing the transcription (TX) and translation (TL) machinery of a living system and combined with plasmid DNA, proteins of interest are synthesized in a tube within minutes. A new generation of myTXTL, introduced at the end of 2018, now lets users harness linear DNA as a template for protein synthesis.
What’s the advantage? Thanks to advances in DNA synthesis, linear DNA is abundant. Companies like Twist and IDT churn out thousands of error-free genes and gene fragments per day and ship them to customers all over the world. Plus, molecular cloning techniques such as Golden Gate Assembly are commercially available as ready-to-use kits, opening up new avenues to easily mix and match DNA fragments into linear genes. Plug those into Arbor Biosciences’ latest myTXTL system and you can be making protein before lunch. “Linear DNA expression is cutting days off the traditional gene cloning process,” says Matthew Hymes, marketing director at Arbor Biosciences.
The reaction runs off of just DNA, a master mix, and water, and can thus also be automated and miniaturized. Evelyn Eggenstein, PhD, product development scientist at Arbor Biosciences, currently leads a collaboration with Labcyte, a leader in high-throughput sampling processing. “We aimed to demonstrate that our master mix, being very complex in its composition, can be consistently dispensed in very small volumes with Labcyte’s liquid handler. There is a great synergy between these two revolutionary technologies in synthetic biology,” says Eggenstein.
Where we’re going, we don’t need cells
Skipping technical steps like molecular cloning (where a linear piece of DNA gets stitched into a circular plasmid) and traditional cell-based expression pays the highest dividends during complex high-throughput experiments, explains Eggenstein.
“[The number of steps] becomes really important if you’re screening more than just one construct a day,” Eggenstein says. With Arbor Biosciences’ new expression platform, “you can perform enzymatic analysis right from the lysate without the need for cell lysis.”
Making the unfathomable fathomable
Arbor Biosciences believes tight coupling between cell-free expression and high-throughput screening will both accelerate and simplify synthetic biology and biotechnology in general. “That’s where our main focus is,” Hymes tells me. “With rapid cell-free expression, more proteins can be designed, produced, and investigated for diverse applications.”
“All of the bottlenecks have been removed from design through protein and enzymatic analysis — even in a very high-throughput manner,” says Hymes. “We’re talking to people that want to screen 5,000 to 10,000 gene fragments a month. That used to be unfathomable when cloning was necessary.”
The streamlining of synthetic biology appears to be happening right on time. Procter & Gamble, BASF, and several other Fortune 500 companies now see the benefit of bio-based manufacturing, both for the planet and their own bottom lines. For biology to truly disrupt business-as-usual at these mega-firms, it must continue to follow the path of computing by becoming both more powerful and easier to use.1