Tuesday, October 4, 2022


Biotechnology News Magazine

Protein Discovery Problems Solved by Michael Chen, Co-founder & CEO of Nuclera

Nuclera eProtein Desktop Bioprinter Product scaled
Imagine screening, characterising, and printing any target protein in just 24 hours right at the benchtop.

Drug discovery and general life science research depend on the ability of scientists to express, purify, and characterise proteins. Despite the importance and size of the protein marketplace — worth over $21 billion in 2019 according to Allied Market Research — the expression and characterisation pipeline for proteins remains a nightmare. Getting proteins is difficult, time-consuming, irreproducible, know-how intensive, and expensive.

I experienced this nightmare first-hand when it took me four years to make the protein necessary for my PhD project. In my conversations with researchers and drug discovery practitioners, this pain is in protein laboratories everywhere. The consequence? The delay of life-saving, next-generation therapies to patients.

What if printing proteins were just like using a 3D printer? 3D printers have transformed the way we prototype parts in workshops and even homes. The drive to create a “3D printer” for proteins spurred me and fellow schoolmates Jiahao Huang, Gordon R. Herling-McInroy, and Radu Lazar to found Nuclera in 2013. We were later joined by co-founder and NGS pioneer, Tobias Ost, as well as the founder of our US operations and E-paper pioneer, Richard Paolini, in 2019 and 2021, respectively. We all wanted to make proteins accessible to everyone through desktop bioprinting – to digitise the wet lab experiment into an easy-to-use, reprogrammable cartridge – shrinking all of that workflow down into a single device. And that device is now coming to reality through our eProtein™ Desktop Bioprinter.

Launching later this year, our desktop bioprinter—the first of its kind—will automate the entire protein expression/characterisation pathway with the use of digital microfluidics – turning DNA into 100µg of target protein in just 24 hours. That’s up to four years condensed into just 24 hours and all you have to do is add DNA into your cartridge. eProtein then screens up to 24 DNA constructs against eight cell-free protein synthesis ‘flavours’ that resemble prokaryotic and eukaryotic organisms enabling 192 screening conditions. The bioprinter then performs a solubility assay for each of those conditions, choosing a ‘winner’ based on rankings. That protein can then be scaled-up directly on the cartridge, automating the purification steps resulting in next-day purified protein.

As you can imagine, the ability to print proteins could be transformative for many life science and biotech sectors – from a large established pharmaceutical company down to the small startup in a garage.

Drug discovery – reducing the time to clinic

We think that making proteins accessible is a key step to making drug discovery accessible and as such, one of the core aims of this technology is to facilitate drug discovery. Not only will the ability to print any target or therapeutic protein significantly reduce time to clinic for many pharma R&D programmes, the desktop bioprinter can also significantly help smaller biotech outfits working on rare diseases, for example. The labour-intensive protein production workflow hits these smaller groups harder, consuming a large proportion of budget and people-hours. With eProtein printing technology, research can be streamlined with increased screening throughput and production capabilities – helping these smaller groups to ultimately partner with larger pharmaceutical companies and bring their important therapies to market more rapidly.

Getting biotech start-ups off the ground

Condensing protein production down into an automated 24-hour process could also have major benefits for innovation and biotech start-ups. Currently there are two main obstacles to growing a biotech research group. First, you need at least a decade of education, training and experience to be able to perform protein expression/characterisation. Second, the capital required to purchase the necessary laboratory equipment numbers in the hundreds of thousands to millions. eProtein printing requires only basic training and negates the need for masses of specialised lab equipment currently required to carry out the protein discovery workflow. Empowering more small-scale protein research start-ups through our bioprinter will help to accelerate discovery.

Accelerating industrial protein engineering

The manufacturing industry produces masses of proteins every year to go into consumer goods from household cleaners and detergents to dietary and skincare supplements. Such products often contain enzymes such as proteases, nucleases and lipases, and these need to be highly engineered for their specific purpose. Our desktop bioprinter could help to select the best candidate proteins for these purposes, and streamline the characterisation and prototyping process as well as accelerating production time.

Agbio discovery

Agricultural biotechnology companies perform a great deal of protein expression and characterisation, and suffer many of the same issues faced by the pharmaceutical industry. Proteins designed for pesticides need to be effective against pests, while remaining unharmful to wildlife and biodiversity. Desktop protein printing could help agricultural biotechnology research companies discover more effective pesticides and herbicides with increased screening capabilities. This may in turn help revive the population of pollinating insects.

With the first ever protein printer we’re trying to make protein discovery as easy and accessible as possible. The prospect of 3D protein printing is now a reality, and we are excited to see how our users do things on our bioprinter we could never have imagined. Because the eProtein desktop bioprinter cartridge is programmable, our community of users have the freedom to adapt and evolve, perhaps even developing their own amazing apps on our platform. This technology could help us move towards personalized medicine printing or decentralised therapeutics. While these are possibilities for the future, the automation of protein production can today provide tangible benefits for drug discovery and R&D across many sectors.

Editor’s Note:  About Michael Chen, Co-founder & CEO of Nuclera

Michael is first and foremost a scientist. He completed his PhD at the University of Cambridge and the National Institutes of Health where he used X-ray crystallography to study the interactions of proteins and nucleic acids at near-atomic level resolution. Prior to his PhD, Michael completed his BSc at the Georgia Institute of Technology in Chemistry. Michael and his fellow co-founders met in the lab during their PhD training. Their first-hand experience at the benchtop advances the product ethos at Nuclera of design by scientists for scientists.  Alongside his team, Michael works to ensure Nuclera’s products make proteins, and ultimately biology, accessible. www.nuclera.com


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