DNA ‘Lego’ to accelerate biodrug production say scientists
The system, called BASIC, uses standardized DNA parts that, like Lego, have the same joining device, so parts will fit together in any order. The system does not address de novo synthesis of DNA; it is not for base-by-base writing, but deals with reordering and joining up small parts to create large DNA constructs
“If you want to develop new biological system or new metabolic pathways to create new drugs, much like artemisinin technology that Amyris pioneered, you start by putting together pieces of DNA,” according to Geoff Baldwin, lead author from Imperial College London, UK.
The approach can draw on a large database of standardized parts, which can be produced in bulk and stored as required, rather than recreating new parts each time.
“Once you have those parts in your freezer, you can now rapidly re-organise them and re-manufacture different combinations of the pathway you are trying to create” Baldwin explained.
“It is a way of stitching together parts from 150 bases up to several kilobases, so the overall construct could be tens of kilobases by the time you are finished,” he said.
DNA linking
The BASIC system has advantages over others in being able to put multiple pieces of DNA together simultaneously. “We successfully stitched up to seven different parts of DNA together,” says Baldwin.
“The more complex system you want to design and build, the more pieces of DNA you have to put together. If you must put those pieces together one at a time, that significantly slows down the process. Putting multiple pieces together really increases the speed and efficiency of the assembly pipeline.”
The technique could offer industry a way to automate the design and manufacture of DNA and it has been developed as an open source method.
“It is purely an enabling technology and the idea of creating it as open source is that we don't want to have patent thickets around putting pieces of DNA together. It should be an enabling technology, where the value is in what you make, not how you make it,” Baldwin said.
BASIC is set to be used in a high throughput automated process in SynbiCITE, the innovation and knowledge centre based at Imperial, which is promoting the adoption of synthetic biology by industry. Two industry partners – Dr Reddys and Isogenica – are making use of BASIC in their research labs already. BASIC stands for Biopart Assembly Standard for Idempotent Cloning.
“Currently we are doing this by hand on the bench and we can build tens of constructs, but for industrialisation you need to be able to build thousands. Our next step is to implement this on a high throughput robotic platform that will make this possible,” said Baldwin. “And that will be available through industrial collaboration.”
Four-part assembly achieved 99% accuracy. Seven-part assemblies achieved 90% accuracy. The present paper tested the system on test constructs, different combinations of fluorescent proteins, but the team is now working on applying it to a metabolic pathway and optimizing it.
Source:ACS Synthetic Biology
DOI: 10.1021/sb500356d
