The combined team from Aalto University and the University of Helsinki, under the leadership of Veera Kurki and Melissa Hendren, addressed a global issue: chronic wounds.

In the previous iGEM competition, the Finnish team had grand visions for their project. They had a great idea, an ambitious plan, and a lot of excitement for what they could achieve.

Their project, named QBlock, aimed to stop the formation of biofilm on chronic wounds by targeting the communication process between bacteria, a process known as quorum sensing. The team set out to create a library of DARPins, that work by binding to the signaling molecules produced by Staphyloccus epidirmitis, a type of bacteria found on the skin.

However, as with any scientific endeavor, things didn’t go exactly as planned. The team initially wanted to create large libraries of fragments, but the cost to complete all of the fragments that they had originally designed was prohibitive. The team hit another roadblock. They realized that manually creating the initial number of constructs was taking much longer than they had anticipated.

It was around that time that they learned about the BioXp® system and its ability to synthesize DNA fragments and automate the cloning process. They were able to use the BioXp instrument that belonged to Immuno Diagnostic – a Finnish distributor of biotech instruments – and with the help of Telesis Bio, the iGEM team installed the instrument in their lab until they were able to complete their project.

“The process of ordering the reagents and getting them to Finland was smooth, and once we had the machine installed, the fragments were synthesized and cloned overnight” – said Melissa, Team Co-lead.

The team purified the DNA obtained from the BioXp system, performed ribosome display, and sent the fragments for sequencing. They used a GFP-binding DARPin as a proof of concept and put some of the DARPins they had synthesized within that same mixture to see if there was competitive binding.

They confirmed that the workflow was working by identifying the DARPins that were binding to the target molecule. They continued with further experiments to optimize and test the activity of the identified DARPins.

The team’s hard work paid off in the end, as they were able to present their project at the iGEM competition and received positive feedback from the judges, who noted that the project was interesting, ambitious, and innovative.

The team’s experience at the iGEM competition is a great example of the challenges and triumphs that come with scientific research. The team encountered obstacles, but they were able to adapt, overcome and achieve their goals.

They also gained hands-on experience with cutting-edge technology, and learned valuable skills in time management and adaptability. Their success story is an inspiration to other young scientists and researchers, and a reminder of the importance of support and collaboration in achieving success in the field of synthetic biology.

As new participants embark on their journey towards a new iGEM competition from Nov 2^nd to Nov 5th, 2023 Telesis Bio is sending a shoutout to all. Best of luck to each one of you!

To learn more about how Telesis Bio is empowering researchers with the tools to build biology in their laboratory, without any constraints, visit our website: www.telesisbio.com.

The post From Challenges to Triumph: iGem Team’s Success Story with Telesis Bio and the BioXp® System appeared first on Telesis Bio.

BioXp system

How do complex targets challenge antibody development pipelines?

Nearly one-half of all FDA-approved drug targets are for GPCRs and ion channels. In a recent survey of top challenges in the field, difficult targets and the selection and screening required to identify leads against them accounted for nearly 80% of all responses. This means that antibody development pipelines had to adapt to meet this demand by embracing not only emerging technologies but also enhanced screening methodologies and higher workflow efficiencies.

What’s the BioXp system and how does it improve efficiencies across antibody discovery workflows?

The BioXp system is the world’s first fully automated synthetic biology workstation and provides a turnkey solution for generating gene fragments, clones, variant libraries, and mRNA starting from just a digital sequence. With all instrument builds taking less than 24 hours, the BioXp system enables numerous synthetic biology applications and is transforming workflows across antibody therapeutic development pipelines. The BioXp system enables researchers to build biology overnight.

Can you describe the BioXp workflow?

The BioXp system workflow is quite simple. First, you submit your digital sequences through our ordering portal. Next, you receive your BioXp kit, which will contain all the necessary consumables for your project. Then you load the instrument, which takes no more than a few minutes, and then finally press start. The BioXp system does the rest. Simply retrieve your products off the instrument and proceed to downstream experimentation.

Can you take me through the process of building and cloning DNA on the BioXp system?

The BioXp system constructs de novo synthesized DNA fragments up to a combined total of 7.2 KB in length and then clones them via Gibson assembly method into the linearized vector of your choice. Up to four unique fragments may be assembled into the final construct.

In particular, the two-fragment assembly cloning workflow provides an easy way to synthesize scFv fragments overnight by building VH and VL segments joined via a linker. If you would prefer to do your fragment cloning manually on the bench, up to 32 unique gene fragments can be built with each BioXp system run.

When compared to industry standard turnaround times for gene synthesis providers how much faster can the BioXp workflow enable time from sequence to transfection?

60-80% faster. Under ideal circumstances with synthesis providers, our customers have mentioned that they can receive the requested products within 2 weeks. Under typical circumstances, the turnaround times can take a month. With the BioXp system, this can be accomplished in less than one week.

How are Telesis Bio’s variant libraries designed for optimal results?

DNA synthesis time is independent of design complexity, constructs are built to specification (not as pools), every sequence is known from design, and there are no molecular biology constraints on protein engineering designs.

How has Cellibre been able to speed up its enzyme engineering process with these DNA libraries?

Cellibre is an agricultural biotech looking to address supply chain issues via bio-fermentation. They have partnered with our team to build multiple complex library designs for their enzyme evolution work. Not only were they able to engineer an enzyme with five times the activity of their starting one, but more importantly, they were able to drastically reduce the build-test cycle to weeks instead of months. Furthermore, they were able to rapidly synthesize complex designs that they were unable to obtain from other DNA synthesis providers.

Interested in learning more about how you can speed up and optimize your synthetic biology workflows? Visit our website to see how you can benefit from Telesis Bio’s synthetic biology solutions.

The post Optimizing production workflows with the BioXp™ system appeared first on Telesis Bio.

Team member: Ken Williams, Bioinformatics Scientist Lead
Came aboard: February 2020

What do you do at Telesis Bio?

I develop the algorithms for the complexity checker, codon optimization, sequence synthesis, the SOLA (enzymatic DNA synthesis) project, DNA data storage, biosecurity, and NGS analysis. In addition to that, I also help troubleshoot customer sequences and I help with the design for myBioXperience, our new online portal we recently launched.

How did you get into that kind of work?

When I was a teenager, both of my parents got very sick. My dad caught a cold that I gave him which led to him developing Guillain-Barre syndrome, so all his antibodies started attacking his neurons. At the same time, my mom was also diagnosed with myotonic muscular dystrophy. I then lost about half of my family on my mom’s side to myotonic muscular dystrophy, which is what led to me being interested in molecular biology and genetics. As far as bioinformatics, I accidentally fell into it since it was the only biology program not impacted at UCSD. The great thing is I ended up liking it much more than being on the bench, which worked out quite well.

How would you describe the company culture?

We’re currently in a transition right now going from a startup to a small company. Ultimately, it’s a fun place to work, we have a huge diversity of work that we’re doing. It’s great that everyone is approachable and easy to talk to. We also have spontaneous events that dictate the culture of the company. I also like the people here who come from diverse backgrounds and bring different perspectives and expertise.

How would you describe synthetic biology to non-scientists?

Synthetic biology is essentially the catalyst to the future because we’re greatly able to expedite research for drug discovery. We will be able to cure diseases. We can do things like engineer algae and solve the climate crisis. We can even store data on DNA using synthetic biology.

What’s something fun about working at Telesis Bio?

There are so many projects that we’re working on. I enjoy interacting with so many people and expressing so many ideas to the various team members. I also like that’s a smaller company because everyone can make an impact.

What was the first thing you ever wanted to be when you grew up?

I wanted to be a civil engineer because I’m interested in that and there are so many moving parts and ways to optimize the way cities are built. I also wanted to be a front man for a thrash metal band.

How do you see synthetic biology changing the world?

Helping with drug discovery, curing diseases, alleviating the climate crisis, and really the possibilities are limitless.

The post In our DNA: Ken Williams, Bioinformatics Scientist Lead appeared first on Telesis Bio.

BioXp system

It has never been easier to build biology in the lab. The award-winning BioXp 3250 system accelerates the design-build-test phases of the product development cycle by automating high-throughput synthesis of genes, clones, variant libraries, and mRNA. A biopharmaceutical company automated the building of expression constructs for chimeric antigen receptors and increased its pipeline by 25% for an antibody-based therapeutic. Additionally, the Depicker lab at Ghent University harnessed the power of the BioXp to address the use of nanobodies as a novel delivery vehicle for more effective vaccine designs. They teamed up with Telesis Bio’s expert services team to streamline the construction of variants, replacing manual cloning methods that had been slow and labor-intensive. See the full case study here. Learn more about how your lab can benefit from complete workflow control for synthetic DNA and mRNA.

BioXp Biofoundry Services

Customers using our variant library services receive high-quality libraries with accuracy, precision, and scale, in days instead of weeks. Generating libraries with Telesis Bio allows scientists to draw conclusions faster, freeing up their time to focus on other discoveries in the lab. For example, scientists from a biotech company recently partnered with Telesis Bio to engineer a recombinant protein with five times the activity of the wild-type sequence and reduced project timelines to weeks instead of months.

Benchtop Reagents

Telesis Bio empowers scientists with high-quality reagent solutions backed by Gibson Assembly® technology. Gibson Assembly Kits incorporate the most trusted technique for generating high-fidelity DNA. Don’t take our word for it — there are more than 4,400 citations validating the use case for the Gibson Assembly method, and the list keeps growing.

RapidAMP® kits leverage isothermal amplification to assemble and amplify transfection-ready DNA in a simple two-day workflow. Achieve up to 10 µg of high-quality, high-fidelity DNA with RapidAMP technology, and skip the tedious tasks associated with transformation, cell culture, and E. coli harvest.

In August, Telesis Bio announced a collaboration with researchers from the University of Florida, UC Riverside, the USDA, Cornell University, and Agrosource to identify scalable therapeutic measures against citrus greening disease. This insect-borne bacterial disease is ravaging the $10 billion citrus industry in Florida, Texas, and California, and left unchecked could destroy the U.S. citrus industry. Our Vmax X2 product line will be leveraged as a scalable therapeutic molecule discovery and production platform to enable rapid and cost-effective screening of biomolecules effective against the disease.

Contact the Telesis Bio team today to find out how we can support your lab work with our automation solutions.

The post Empowering Scientists to Make Breakthrough Discoveries to Address Humanity’s Greatest Challenges appeared first on Telesis Bio.

BioXp system

These latest improvements come from our partnership with scientists at TriLink Biotechnologies, part of Maravai LifeSciences, and incorporating their industry-leading CleanCap^® technology into our suite of automated mRNA synthesis kits for the BioXp system as well as our BioFoundry Services offering.

Our new BioXp small-scale mRNA synthesis kit with CleanCap reagents is expected to overcome many challenges associated with the development of mRNA-based therapeutics and vaccines by increasing the yields and productivity of synthetically designed mRNA products. Conventional techniques for building mRNA require a fully manual, multi-step process that is tedious and often fraught with technical difficulties and bottlenecks that require long turnaround times.

Now, Telesis Bio customers will have the option to generate up to 16 biologically active mRNA constructs at a yield of at least 10 micrograms each from fully de novo synthesized and error-corrected genes in a single automated run. These combined technologies increase the fraction of translationally active mRNA during transcription, which simplifies and shortens the mRNA manufacturing process and results in higher levels of protein production.

Learn more about BioXp workflows for mRNA synthesis.

The post With <span class="lowercase">m</span>RNA Capping Technology, We’re Improving Synthesis Yields appeared first on Telesis Bio.

BioXp

Over the years, Lytic polysaccharide monooxygenases (LPMOs) have attracted considerable attention due to their implication in lignocellulosic biomass decomposition to produce biofuels and high-value chemicals. Their unique and powerful oxidative abilities make them promising targets for enzyme engineering. However, there are major challenges to produce active LPMOs, like low yield from native hosts, lack of purity and cultivation obstacles; therefore, recombinant production of LPMOs in the model organisms is highly desired.

Researchers at the Norwegian University of Life Sciences harnessed the benefits of the BioXp automation solution. After the design of the expression plasmids, they synthesized the LPMO genes and cloned them into the plasmids following the industry standard Gibson assembly method. Both steps were conducted on the streamlined BioXp automation workstation with a simple push-button workflow. The whole process from sequences to cloned plasmids takes less than 8 hours. The output of the BioXp run was in total eight plasmids with either the pBYSP_GCW14Z or the pBYS3Z expression plasmid into which one of the four LPMO genes had been cloned. Both high yield and purity were achieved. The shortened engineering cycle for the highly expressed LPMO system enabled researchers to rapidly discover and modify desired features for efficient protein production. Unlike the manual process with which individual plasmid is built, BioXp system can build up to 32 genes in four different vectors simultaneously in one run. Additionally, the automation process also alleviates potential operation errors and improve reproducibility. BioXp system offers a powerful tool to unlock the power of synthetic biology and enable sustainable solutions for our future.

Learn more

The post Unlock the potential of BioXp™ automation solutions for bio-fuel production appeared first on Telesis Bio.

To achieve this goal, they are abandoning the economically inefficient model of growing plants, to harvest key extracted and isolated compounds like CBD. But knowing that cellular manufacturing for cannabinoids will be superior to plant-based products is one thing; accomplishing it is quite another.

Cellibre scientists teamed up with the Telesis Bio service group, allowing them to identify a novel enzyme for cannabinoid production and hone its performance using targeted libraries from Telesis Bio — doing so much faster and more cost-effectively than any other method would have allowed.

“Targeted libraries allowed us to make very complex designs that we normally would not be able to test, because each design would have to be built individually, by de novo synthesis, costing far too much, or as huge pooled libraries containing mostly variants we aren’t interested in,” says Russell Komor, director of biochemistry at Cellibre. “The Telesis Bio approach gives us whatever mutations we want, and the data we get are so much more powerful and more predictive.”

Komor’s team found that the optimal candidate was one they couldn’t have designed any other way. It included three mutations that separately were not all highly beneficial, but together had excellent performance.

“In the past, our recombination designs would need to be modified to fit the molecular biology tools needed to build them,” Komor says. “Now, we’re making any designs we want, and we don’t have to worry about the molecular biology. This really allows protein engineers to focus on engineering.”

To learn more about this project and see data about enzyme performance and more, check out the full case study.

The post Case study: How Cellibre transformed enzyme engineering with Telesis Bio appeared first on Telesis Bio.

Bacterial resistance to antibiotics is a looming public health crisis, and scientists continue to investigate how to better characterize the molecular mechanisms underpinning this threat.

A team from the National Cancer Institute reported exciting progress on this front in work that relied in part on our BioXp system for automated DNA synthesis.

Their findings fill important gaps in our understanding of how E. coli and related enterobacteria dodge antibiotics and other cell membrane disruptions. “Bacteria must constantly monitor the integrity of their cell wall and envelope to withstand environmental insults,” write authors Erin Wall, Nadim Majdalani, and Susan Gottesman in their PLoS Genetics publication. A key element in that defense system for enterobacteria is known as the Rcs phosphorelay, but its regulation was poorly understood.

After a series of impressive experiments, the scientists have now elucidated much of the process — including how a regulatory protein in the inner membrane, IgaA, adjusts signaling in the Rcs pathway. “We performed in vivo interaction assays and genetic dissection of the critical proteins and found that IgaA interacts with the phosphorelay protein RcsD, and that this interaction is necessary for regulation,” the scientists write. They also found that a second interaction is necessary, and that a single point mutation in the relevant domain “increased interactions between the two proteins and blocked induction of the phosphorelay.”

Some of this pathway characterization was performed with a novel reporter assay that detects expression of a small RNA associated with Rcs regulation. The in vivo fluorescent assay proved to be sufficiently sensitive to track this key marker. With results from the assay and other analyses, the team determined that “the multiple contacts between IgaA and RcsD constitute a poised sensing system, preventing potentially toxic over-activation of this phosphorelay while enabling it to rapidly and quantitatively respond to signals.”

Here at Telesis Bio, we were delighted to see that the scientists used synthetic DNA constructed with our BioXp system for the alanine-scanning mutagenesis part of this project. They were able to design and test 35 “single mutants targeted at conserved residues within the cytoplasmic region of RcsD,” as they note in the paper. They chose several mutants with expression levels matching their control sample for followup analysis.

We congratulate these scientists for their terrific work and look forward to seeing how the research community can build on their important findings.

The post Scientists use automated DNA synthesis to identify response to antimicrobial threats appeared first on Telesis Bio.

BioXp system

In the preprint, lead author Olivia Swanson and collaborators report “a new approach that relies on computational modeling to identify the functionally important somatic mutations present in HIV [broadly neutralizing antibodies] and a strategy to identify and validate candidate immunogens that select antibodies with these mutations in vitro.”

The team reviewed the many acquired mutations characteristic of HIV antibodies to identify the minimal subset required for the intended response. In this case, just 12 of the 42 mutations analyzed in a specific antibody lineage were needed to achieve potency. They then designed an antibody containing only those mutations, positing that it represented an “evolutionary path that is shorter and less complex to induce by vaccination.”

In addition, the scientists came up with a new immunogen design method “that relies on high-throughput screening of antibody libraries to identify envelopes that interact with DH270.6-derived antibodies through the key acquired mutation,” they write.

For this project, researchers deployed the automated BioXp system for DNA synthesis of a pooled oligo library. The library was then sorted according to binding affinity for five HIV envelopes, and the best performers were sequenced to compare enrichment levels of key mutations.

“This work illustrates a general approach to identify key functional mutations… and describes a high-throughput method to rationally discover immunogens that target antibody functional mutations,” the authors report.

The post For HIV vaccine study, scientists build pooled variant library using automated DNA synthesis appeared first on Telesis Bio.