Category: Services

Parent category for Ginkgo’s service areas

Protein Expression Services Q&A

Posted on by Ginkgo Bioworks

Sneha Srikrishnan, Director of Growth, Business Development at Ginkgo Bioworks, is here to answer your burning questions around our new offerings in protein expression!

This conversation was moderated by Annick Saralegui, Senior Marketing, Growth Specialist at Ginkgo.

To kick things off, tell me, what does Ginkgo have to offer for customers developing proteins?

Sneha Srikrishnan: This is super exciting! So we have four different modules of work that we would like to repeatedly use to help our customers in protein expression wherever they are in the R&D cycle. The 4 include:

  • Host evaluation: evaluate and compare your host strain with our suite of hosts
  • Strain optimization: optimize your strain with genome modifications for better quality, functionality, and titer
  • Classical strain improvement: use non-GM approaches to push titers higher 
  • Scale + fermentation: access our pilot and commercial scale fermentation facilities to increase production efficiency all in-house

For the first module, host evaluation, does this mean I can bring my own strain to Ginkgo? If I’ve spent a few long-and-hard years designing a host, can Ginkgo work with my strain?

Certainly! We can now engineer customer strains as much as we can engineer Ginkgo chassis strains. So that’s number one. 

And what that means is, if our customers have strains that they really like and they enjoy using, bring it to us! We can improve on it and help them get to higher titers, provide better functionality, and even improve on process media optimizations or process development for those strains.

In the early days at Ginkgo, we were more comfortable just working with Ginkgo strain backgrounds and now we’ve opened doors to customer strain backgrounds. And why? Because we recognize that our customers have put a lot of time and effort into their R&D and their strain backgrounds and have invested in CapEx to build processes that go along with their strains. So instead of backtracking and eliminating the body of work that’s already been invested in, we can add to it.

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Let’s say I’m not too sure what strain I should use, mine or Ginkgo’s. Can Ginkgo help me make the right call to reach my goals? 

Yes. We can now perform host strain comparisons – early on. 

That means if anyone is starting early on and doesn’t know whether to invest in a fungal strain background which is filamentous in nature, like a Trichoderma or an Aspergillus, versus say a Pichia we have, we’ll run in a host evaluation body of work, which is very quick.

It can be run within six weeks, maximum eight weeks, to provide a high level feedback on whether Pichia or the others have better better titers and are able to be a good match for being a production organism. So it gives you quick feedback and this can help with early stage GRAS filing.

Let’s say I’m a prospective customer and I’d like early access to a protein sample. Is this something Ginkgo offers?

Yes, that’s very new!  If anybody wants protein samples to try and test for functionality during a strain engineering program, we’re willing to provide them with samples. These can be generated from ambr250 system fermentations or from 5L fermentations or even higher.  

What I’ll also mention is Ginkgo has invested in building out our scaling facilities so that we can even run strains at a commercial scale. Why is this important for the protein world? 

Under one roof, we have the ability of generating up to 10 grams of sample, if not at the kilogram scale when run at 3000 liters.

It can all be done in-house and this is very exciting because our partners can essentially receive samples, do some functionality testing, and if there’s anything to be changed from the same strain background to meet specs, we will now be able to fix the strain and not lose time in the process. So it’s time gained. 

What’s so special about Ginkgo’s strain assets especially for, as an example, alternative food protein production? 

I’m excited because we have developed cutting-edge strains for very special and complex, hard-to-engineer proteins such as iron-bound proteins. We’ve spent a lot of time determining how to modify the strains’ post-processing folding machinery in order to improve the titer and functionality of proteins.

So we’ve basically created a suite of strain backgrounds that can accommodate multi-copy integrations and codon optimization. We also have proprietary synthetic promoter systems that will allow for tunable and controllable expression which are not methanol-based. So methanol-free is based on simple carbon sources, which have very good COGS in terms of raw material usage.

We also have synthetic secretion signals for secreted protein. If you want to keep it intracellular, we can keep it intracellular and we’ve also developed a suite of strains which have unique helper genes or co-expression genes such as chaperones and protease knockouts.

Why is this important? Because we figured out ways in which the helper genes will help, post-translation, to package the proteins and help translate them across the ER, and then across the cell wall.

Essentially, we have identified unique ways to not just produce a protein but also to keep it stable once it’s secreted.

So all of this can be done in short spans of time. We have examples where we’ve run dairy-protein type projects. The first time we generated these strains, we invested close to 15 months worth of pre-work to generate the strains.

Because of the pre-work we invested, When we partnered with clients that needed iron-bound proteins, we were able to get from a single digit gram per liter, very quickly up to in the range of 5+ gram per liter scale for dairy protein within six months, which is significant time savings.

Can I test for functionality with Ginkgo?

We have some capability to test functionality within Ginkgo for a subset of samples. And if we are unable to run those functionality screens in-house, we have partnerships set up where we could be outsourcing to our partners for functionality screens for food proteins.

Assays such as iron binding can be done within Ginkgo.

Antimicrobial activity can be done within Ginkgo other more specific assays such as: melting temperatures, aggregation temperatures can also be done at Ginkgo. If there are more specific assays required, we can outsource to our partners.

I’m a prospective customer and have heard of EncapS and ALE.  EncapS for Encapsulation & Screening and ALE for Adaptive Laboratory Evolution. Can you explain that a bit more and how I can leverage those services for my project?

The EncapS strategy would normally work if you have a strain that’s already making something. If you have a strain that’s making a product of interest or a protein of interest, and it’s making a very small amount of the protein and you want to get to multifold improvements very quickly, then go with EncapS.  So with EncapS, what we can do is when you are already at reasonable titer in the gram per liter range, we can increase titers by 20, 30 percent or sometimes even reach 50 percent improvement.

We can run multiple rounds of classical mutagenesis or generate a library of semi-rational mutants. That semi-rational mutant library can then be quickly screened through encapsulated cells within nanoliter beads. And we can screen over 1 million clones in a single round.

Why is this useful? because when you screen for a million clones you can quickly get titer improvement jumps.

EncapS can also help you achieve better strain productivity.

We will essentially not just look for a high protein titer, but we’ll look for improved productivity.  So we’ll directly read out for secreted protein, as well as the biomass.

Why is this good? Because you not only want to have high titer, you also want to have decent microbial growth. Otherwise your fermentation will be challenging. So if you want to have good productivity, you look for both good biomass and good protein titer. The EncapS method can help you look for both.

Now, where does ALE come into picture, if you want to switch carbon sources?

So let’s say that you have a strain that is going to grow on waste material and you want to circularize the process. You want to do waste valorization and you want to pick up C5 sugars in addition to C6 sugars. Then ALE is a great way to change the carbon preference or to open out the carbon preference as an example for the organism that’s already making something of your interest.

If you’re looking for change or improvement in the growth rate specifically then it can be considered. That’s how I would use it.

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Synlogic Leverages Ginkgo’s Cell Engineering Platform to Develop Potential New Treatment for Homocystinuria

Posted on by Sudeep Agarwala

Interested in leveraging Ginkgo Enzyme Services for your R&D? Get in touch here! 

Executive Summary:

Synlogic designs and develops Synthetic Biotics — living biotherapeutics based on engineered bacteria — with the potential to provide safe, convenient, orally-administered, non-systemically absorbed new medicines for serious diseases. The company has a focus on rare metabolic diseases, including homocystinuria (HCU), which is characterized by elevated levels of total homocysteine (tHcy). Patients are at risk of both acute, life-threatening events and severe complications. HCU treatments aim to reduce tHcy levels in patients, firstly through limiting intake of methionine, an amino acid precursor to homocysteine found in many foods. Synlogic recognized the potential of methionine as a target for a Synthetic Biotic and partnered with Ginkgo to improve the activity of their initial prototype biotherapeutic candidate.

Synlogic and Ginkgo set out to increase the activity of methionine degradation, focusing on the key enzyme Methionine Decarboxylase (MetDC). Leveraging Ginkgo’s Enzyme Intelligence suite of tools, Ginkgo delivered genetic parts that multiplied methionine degradation activity in vitro, including a new MetDC enzyme with more than four-fold higher activity. Within a year of initiating the program, Synlogic incorporated these components into their prototype strain and evaluated the activity of the optimized strain, SYNB1353, in mice and nonhuman primates.

Opportunity | Developing living medicines for a genetic disease

Based in Cambridge, Massachusetts, and founded in 2014 by MIT professors Jim Collins and Tim Lu, with support from Atlas Ventures, Synlogic designs living medicines for diseases with significant unmet needs. The company uses synthetic biology to genetically engineer probiotic bacteria (Escherichia coli Nissle 1917) and generate living medicines designed to metabolize or synthesize validated biological targets of known disease pathophysiology.

One disease Synlogic is targeting is homocystinuria (HCU), an inherited disorder characterized by risks of elevated homocysteine. The build-up of homocysteine can lead to multiple adverse effects, including bone defects, intellectual disabilities, and life-threatening blood vessel obstructions. Treating HCU aims to lower levels of total homocysteine (tHcy); a cornerstone of treatment is restricting dietary methionine, an amino acid found in protein-containing foods, and which is a precursor of homocysteine.

Joanna, who lives with HCU and has endured two strokes, seizures, and vision impairment because of this disease said, “We need to come together as a community and do more. Nobody knows how devastating HCU can be… We must continue to focus on research and work to develop new treatments. In the meantime, I want those living with HCU to know they are not alone and there are people who want to help.”

Current treatment options for HCU are limited in terms of safety, tolerability, and efficacy, underscoring the need for a new, innovative approach: Synlogic engineered a Synthetic Biotic to target and metabolize methionine as a means of lowering tHcy levels to treat HCU.

Solution | Boosting microbial metabolism for human disease

In developing a Synthetic Biotic for HCU, Synlogic sought to improve two activities of their bacterial strain: the methionine importer that transports methionine into the bacterial cell, and the methionine decarboxylase (MetDC) that efficiently converts methionine into non-toxic compounds to prevent tHcy accumulation.

Ginkgo’s protein engineering team took two approaches to improving these components. A metagenomic approach searched through Ginkgo’s extensive multi-billion protein database for a biologically diverse set of candidate enzymes. In parallel, a protein engineering approach applied predictions from machine learning models in combination with structural analysis to design variants of the two proteins with a high likelihood of improved functionality. Combined, these approaches identified roughly 2,000 candidate methionine decarboxylases, and a targeted library of roughly 150 candidate methionine importers.

DNA for the enzyme libraries was synthesized and transformed into Synlogic’s strain background. In parallel, Ginkgo’s engineers developed a bespoke, high-throughput assay that would test the functionality of the importer protein and MetDC proteins. Once the DNA was synthesized and transformed into the screening background and the bespoke assay was on-boarded onto Ginkgo’s high-throughput automation platform the strains were screened in high-throughput in Ginkgo’s Foundry. The team identified an importer and decarboxylase that, in combination, showed significant improvement over Synlogic’s previous prototype. Synlogic was able to verify that these two new proteins improved their strain’s methionine degradation in vitro.

Outcome | Developing new treatments for human disease

Within a year, Ginkgo’s collaboration with Synlogic resulted in the naming of the investigational new drug, SYNB1353. The drug successfully demonstrated proof-of-mechanism in humans by showing the ability to degrade methionine and reduce its plasma levels using a dietary model. This is the first investigational new drug developed on Ginkgo’s platform. It was granted Orphan Drug Designation, Rare Pediatric Disease Designation, and Fast Track designation by the FDA. Next steps for the program include a Phase 2 study in patients with HCU. SYNB1353 offers a potentially new, orally administered, and non-systemic approach to degrade methionine, thereby lowering tHcy and its associated risks and daily disease burden of HCU.

“As a company, we are in regular contact with leaders and members of the HCU community, who continually express their appreciation for our efforts to bring something new forward,” said Mylene Perreault, PhD, Head of Research at Synlogic. “It is very powerful to hear directly from patients and caregivers about how transformative it would be to have an option that could target and convert methionine, lowering total homocysteine levels in the safe and convenient way that SYNB1353 could provide. Ginkgo has been an important part of this program’s journey and the collaboration that has helped us reach the point of studying this new drug candidate in patients.”

 

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Enhancing Meaty Taste of Mycoprotein with Nosh.bio

Posted on by Ginkgo Bioworks

 

Today we’re so excited to announce a new partnership with Nosh.bio, a German startup developing highly functional ingredients from fungal biomass for animal-free products. Nosh.bio will leverage our Ginkgo Strain Optimization Services to screen for protein-producing fungi strains with superior sensorial profiles. By leveraging Ginkgo’s ultra high throughput encapsulated screening capabilities, the program aims to produce a mycoprotein that delivers a rich, savory, and natural meaty taste when used in food products.

The Challenges with Animal-Free Protein

Companies developing animal-free protein still face challenges in creating tastier, less processed, and affordable alternative-protein products. Nosh.bio has built a technological platform that uses fungal biomass to create animal-free single-ingredient animal meat alternatives from mycoprotein for human nutrition.

For meat-alternatives, red meat — like a juicy steak — remains the most challenging product to be developed, and current alternatives contain many ingredients and chemical additives. Nosh.bio aims to leverage their highly efficient, sustainable, and cost-effective production process to create a single-ingredient animal-free product that tastes and feels just like red meat, while being healthier than an animal product.

Ginkgo Strain Optimization Services

To enable this advanced alt-protein product, Ginkgo aims to discover and deliver a strain of fungi with higher native proteins involved in achieving the rich meat taste, juiciness, and color that Nosh.bio is seeking. To do so, we plan to execute a mutagenesis and screening campaign with our proprietary encapsulation and screening technology (EncapS). This can make it possible to search through up to 1 million strain variants in a single run and select the best performing candidates for further development. Using such an improved strain can help Nosh.bio develop a mycoprotein that is superior in taste, color, performance, and nutrition.

“Nosh.bio is eager to enable the transition from animal-based to animal-free products. Our affordable, high quality plant-based ingredients can build a product that’s even closer to meat in taste and texture than alt-protein options currently on the market,” said Tim Fronzek, CEO and Co-Founder of Nosh.bio. “What really excites us about partnering with Ginkgo is their accelerated screening technology that can help us pinpoint and develop a super ‘meaty’ mycoprotein.”

Leveling Up the Alt-Meat Protein Industry

We’re thrilled to partner with Nosh.bio and help level-up the alt-meat protein industry to deliver sustainable products that taste closer to real meat than ever before. Our proprietary encapsulation and screening technology can expeditiously deliver valuable insights that enable our partners to optimize their R&D efforts and overall product.

To learn more about Ginkgo Strain Optimization Services, please visit https://www.ginkgobioworks.com/offerings/strain-optimization-services/.

Find the full press release here along with all of the latest news from the Ginkgo team.

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Revolutionizing Enzyme Engineering: The Synergy of Big Data and AI at Ginkgo Bioworks

Posted on by Sudeep Agarwala

Interested in leveraging Ginkgo Enzyme Services for your R&D? Get in touch here! 

Enzyme Engineering and Artificial Intelligence: A New Frontier

Enzymes are the heroes of biotechnology, serving as biological catalysts that make life’s complex reactions look easy. Inside of the cell, enzymes direct the flow of molecules through metabolic pathways, orchestrating biological functions. Outside of their cellular context, enzymes have been co-opted for specialized roles in manufacturing, speeding up processes that would otherwise be painstakingly slow. In pharmaceuticals, enzymes are custom-engineered to act as targeted therapeutics. Whether in life sciences or industrial applications, enzymes elevate our ability to engineer processes and enact chemistries by facilitating reactions with speed and specificity.

For years, scientists have used a variety of tools to design and optimize these crucial biological components. Traditional methods have often hinged on exploiting evolutionary pressures—letting nature do the heavy lifting over generations and then picking the winners. Structure-based prediction techniques, like Rosetta, also made a significant impact, allowing researchers to model how tweaks to an enzyme’s structure could influence its activity.

But we’re entering a new era–one in which we can train Artificial Intelligence (AI) models based on large biological data sets. This is where Ginkgo Bioworks comes in. Our expansive cell engineering platform is a data-generating powerhouse, churning out the kind of high-quality, voluminous data that AI algorithms thrive on. The marriage of this large-scale data generation with AI models allows us to transcend previous limitations, making Ginkgo an ideal environment to train and deploy machine learning tools for the complex art of enzyme engineering.

The AI Story: Big Data, Bigger Breakthroughs

AI learns from large data sets. Ginkgo Bioworks generates these types of data: we make it possible for you to produce and learn from large data sets. Our extensive repositories of enzymes not only cover a wide range of protein sequences but are also complemented by highly targeted data, revealing precise sequence-function correlations. This dual-data approach is implemented through machine learning cycles in our enzyme engineering projects, enabling us to iteratively refine predictive models.

Ginkgo has developed an AI tool, Owl, to fine-tune enzymes for a specialized role. An expansive data set provides the foundational architecture. To construct the intricate details, however, we employ data that is calibrated to the specific enzyme and its intended function. This enables Owl, our machine learning tool, to not merely “learn” but to “apply” its learnings, writing the intricate, detailed novel enzyme that our scientists require. Owl can “see in the dark” and discern viable paths in complex enzyme design landscapes.

Ginkgo’s approach to enzyme design isn’t merely data accumulation; it’s strategic data deployment. Our Foundry is equipped to generate an extensive range of high-quality biological data at scale. From DNA design and synthesis to high-throughput screening, we create vast data sets corroborating structure-function relationships. Owl thrives in this environment, allowing us to design enzyme variants tailored to our partners’ unique specifications, whether that’s enzyme activity, specificity, or other parameters.

As we navigate the complexities of enzyme design and optimization, think of Owl as the expert navigator and our robust data sets and data-generating capabilities as the compass and map. Together, they form a symbiotic alliance that not only challenges but also redefines the boundaries of traditional R&D.

Tackling Enzymes in Central Carbon Metabolism: the power of iteration and integration

Enzymes that regulate flux through Central Carbon Metabolism (CCM) are biological masterpieces. These proteins have been shaped by billions of years of evolutionary refinement to execute their functions with unmatched precision and, in many cases, maintain high sequence and structure conservation throughout the tree of life.

In one example of Owl-guided enzyme optimization, we were asked to improve the reaction kinetics of an enzyme involved in CCM. While this enzyme had been studied for the past 50 years, the best improvement we found in the literature was a 2-fold increase in the kcat/KM–catalytic efficiency; our customer needed a 10-fold improvement in the efficiency of this enzyme in order to meet their economic targets.

Our approach to this project leveraged our Foundry’s ability to generate and test large libraries of strains. In our initial data-generation phase, we created a first-generation library featuring 2,000 distinct enzyme variants crafted using a structure-based design, as well as semi-rational methods like active-site mutagenesis for targeted alterations. This is an important step because it generated a data set for initial Owl training. With this information in hand, we designed a second generation library to give Owl more information: we maintained the library size of the first but incorporated insights from the previous round, resulting in an exciting 3.9-fold improvement—a leap that surpassed anything we had seen before.

But the real improvements were just beginning. The third generation of this program brought us to a pivotal point in our optimization journey. Leveraging Owl’s predictive analytics, we strategically developed a broad library of 4,000 enzyme variants, generating diversity where it mattered most. The result was an unprecedented 4.5-fold improvement in enzyme efficiency, serving as a testament to Owl’s growing mastery in predictive capability.

Data from these three consecutive generations positioned us to make our biggest improvements yet. Given the data that our scientists had generated, Owl continued to generate increasingly sophisticated models of enzyme function. The final iteration culminated in a fourth generation where only 100 enzyme variants needed to be tested. The result, which marked the successful completion of this customer program, was astonishing: a 10-fold improvement in enzyme function, verified through meticulous arrayed activity assays and detailed protein characterization. By integrating the large data sets generated by Ginkgo’s cell engineering platform with Owl’s predictive power, we surpassed the bounds of natural evolution and decades of research reported in the literature meet our customer’s targets.

The future of enzyme engineering: large data and machine learning at Ginkgo Bioworks

The confluence of big data and AI accelerates the pace of innovation to unprecedented speeds. Ginkgo’s cell engineering platform is an ecosystem designed for generating expansive, high-quality data sets customized for complex biological inquiries. This data, in turn, fuels the predictive power of AI models. Together, they form a symbiotic relationship that enables us to challenge the limitations of natural evolution and traditional research methods.

As stakeholders in the biotechnology industry, navigating complex R&D challenges requires more than just robust tools; it requires effective partnerships. Ginkgo Bioworks offers the specialized machine learning models and data-generation capabilities necessary to advance your research and overcome bottlenecks. Our suite of resources is designed to integrate seamlessly with your objectives, providing actionable insights and solutions tailored to your specific challenges.

Ginkgo is investing in the future of AI for biotech: see our recent announcement with Google about developing foundation generative AI models for DNA and protein. Leverage our expertise and technology for your next project, and to join us in pushing the boundaries of what is possible in synthetic biology.

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Developing Enzyme for Single-Cell Library Prep Technology with Factorial Biotechnologies

Posted on by Cindy Chang

We’re thrilled to announce our new collaboration with Factorial Biotechnologies, an emerging single-cell sequencing company with a novel intracellular library preparation technology.

Through this partnership, Factorial will leverage Ginkgo Enzyme Services to develop a novel isothermal DNA polymerase for use in their single-cell next-generation sequencing (NGS) library prep kit. Given our extensive expertise in this space, Ginkgo will provide these services under our success-based pricing model, created to help companies de-risk their research and development efforts.

Single-cell sequencing is a promising technique to better understand genetic and functional diversity within complex tissues and biological systems, but its impact has been limited, due to complex laboratory workflows and high cost.

Factorial Biotechnologies aims to dramatically simplify the workflow of single-cell sequencing with an extraction-free technology that makes it possible for complete NGS libraries to be prepared inside of intact cells within a mixed cell population. The potential for this scalable, high-throughput, and cost-efficient technology spans scientific research in the healthcare and life science industries, including precision oncology, immunology, cell and gene therapy, and quality control and screening for synthetic biology. With Factorial’s in-cell library prep technology and barcoding scheme, single-cell libraries can also be prepared using digital PCR workflows.

To support this promising technology, Ginkgo will lead a campaign in P. pastoris to develop a novel enzyme — isothermal DNA polymerase —  instrumental to Factorial’s innovative NGS library prep kit. Our advanced ultra high throughput screening methods can help identify unique enzymes and valuable reagents with desired activity and functions for innovative life science tools and research. Performing discovery and high throughput screening in our proprietary P. pastoris expression system enables synergy between early innovation and manufacturability of these valuable reagents.

“We look forward to working with Ginkgo to develop and optimize a unique and important piece of our workflow. We’re eager to see our cost-effective, high throughput technology help researchers and clinicians deliver on the promise of single-cell genomics.”

John Wells, Co-Founder and CEO of Factorial Biotechnologies

We are so excited to power Factorial’s differentiated technology on our platform. We believe Factorial’s extraction-free library prep will be a game-changer for single-cell sequencing, and we’re proud to help play a part in it. Ginkgo Enzyme Services is uniquely suited to rapidly enable novel molecular diagnostic assays through broad metagenomic searches and efficient AI-enabled enzyme engineering.

Enzymes power a diverse array of applications across industries from industrial processing, chemical manufacturing, therapeutics, as well as applications such as Factorial’s innovation in life sciences and molecular diagnostics. Ginkgo’s platform enables discovery and development of enzymes to enable innovators across industries who seek to make better technologies more accessible.

To learn more about Ginkgo Enzyme Services and how you can access Ginkgo’s success-based pricing, please visit ginkgobioworks.com/enzyme-services/.

Find the full press release here along with all of the latest news from the Ginkgo team.

What will you grow with Ginkgo?

IARPA B24IC Research Contract: Developing Breakthrough Biointelligence and Biosecurity Innovations

Posted on by Jason Kelly

IARPA B24IC Research Contract

We’re pleased to announce that we’ve been awarded a research contract from the Intelligence Advanced Research Projects Activity (IARPA), the research and development arm of the U.S. Intelligence Community, for the Biointelligence and Biosecurity for the Intelligence Community (B24IC) program. Through this program, we aim to develop a biosensor that records time-ordered cellular memory for improved traceability and biosecurity.

A revolutionary biosensor

As a part of the collaboration, we will build on recent scientific breakthroughs to create a revolutionary biosensor that can continuously record and store gene expression data in chronological order within a microbial genome, and to also create processes to retrieve this data to reconstruct the exposure history of a microbe. This tool would allow users to monitor the lab conditions and processes to which the cell was subjected. This cellular “flight recorder” would function as a synthetic memory device, registering cellular histories to support investigations into origination, attribution, and specific use, including excursions into higher/lower temperatures and contact with other substances.

Our ability to computationally design hundreds of thousands of DNA sequences and strains and to physically build and screen them at scale for faster discovery can provide the B24IC program with the capabilities to realize this project’s goal. These capabilities include our capacities in protein design and as well as the engineering expertise needed to develop this genomically integrated DNA-recording system and to build a series of intracellular biosensors that can revolutionize biosecurity through the use of robust cellular memory systems.

“The rapid proliferation of biotechnology stands to pose new national security risks that the Intelligence Community will need to counter and mitigate,” said B24IC Program Manager Dr. Michael Patterson in a recent press release. “B24IC could boost our approach to biointelligence and biosecurity far beyond our current understanding—years or decades into the future.”

Furthering our partnership with IARPA

This announcement deepens our partnership with IARPA to boost the nation’s approach to biointelligence and biosecurity. We have a history of partnering with IARPA, most recently through its Finding Engineering-Linked Indicators (FELIX) program, which was created to augment and improve current biodetection and biosurveillance capabilities. Through the program, we developed a novel computational platform for detecting genetic engineering: ENDAR (Engineered Nucleotide Detection and Ranking).

This project is a milestone for us in our growing role as a trusted biosecurity partner to the U.S. government. We are deeply committed to this space, which you can see in our implementation of large-scale pathogen monitoring infrastructure nationally and worldwide, and in the breakthrough biosecurity tools we’ve already developed to detect and deter the misuse of bioengineering.

The Biden Administration’s Executive Order on advancing biotechnology and biomanufacturing includes an important mandate for all of us in the field to work on advancing biosafety and biosecurity. This is absolutely critical for the growth of the bioeconomy. At Ginkgo, we’re excited to develop biosecurity innovations that have the potential to both keep us safe and drive innovation in responsible bioengineering.

This research is based upon work supported in part by the Office of the Director of National Intelligence (ODNI), Intelligence Advanced Research Projects Activity (IARPA), via N66001-23-C-4509. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies, either expressed or implied, of ODNI, IARPA, or the U.S. Government. The U.S. Government is authorized to reproduce and distribute reprints for governmental purposes notwithstanding any copyright annotation therein.

What will you grow with Ginkgo?

Virtual Event: Functional Food Proteins with Microbial Expression Systems

Posted on by Jake Wintermute

Watch the Event

A recording of the Virtual Event, Functional Food Proteins with Microbial Expression Systems, is available here.

 

Foundry Services for Functional Proteins

On June 30th, Ginkgo hosted a live virtual event to present our latest strain engineering capabilities for food proteins and enzymes. These capabilities support our offering of R&D services for the nutrition and wellness industry and are relevant for anyone seeking to produce functional protein ingredients with precision fermentation.

Strain Matters: Pichia and Aspergillus

The event featured two of our favorite microbial production hosts, Pichia pastoris and Aspergillus niger. Both of these strains have long been favored for protein and enzyme production because of their high productivity, food-safe regulatory status and ability to grow on low-cost feedstocks.

But not all strains of yeast and fungi can perform at the level required for food ingredient production at scale. A key message of the event was that your strain matters: choosing the correct expression host for your protein product can speed up your development times and decrease your final production costs.

Ginkgo offers proprietary strains of Pichia and Aspergillus that can address many of the common challenges of food protein or enzyme production. Two featured presentations during the event described the relative strengths of each strain and a case study in which the strain delivered for a particular customer’s performance requirements.

Pichia is often preferred as a base strain for its easy engineerability and large genetic toolbox. Andrea Camattari, Senior Director of Organism Engineering, presented a recent project in which Pichia was adapted to produce an iron-binding food protein, using proprietary methanol-free expression systems (20-fold higher expression than methanol based promoters). Several strategies were employed to improve the expression and the localization of the needed cofactors, resulting in a host strain that far exceeded the customer’s production targets.

Aspergillus can produce certain classes of proteins at extraordinarily high titer (120 g/L or higher), but has historically been limited in large-scale fermentations because of its high viscosity. Peter Punt, Distinguished Organism Engineer and Guest Professor at Leiden University, described Ginkgo’s proprietary low-viscosity, proteases knocked-out and “clean” background Aspergillus that can produce food proteins and enzymes in high titer.

Technology Matters: Ginkgo’s Foundry

Strain engineering at Ginkgo, whether in Pichia, Aspergillus, or another host organism, is an integrated process that benefits from the full stack of cell programming technologies available on our foundry platform. Sneha Srikrishnan, Director of Growth, surveyed a range of technological capabilities that we can deploy for a customer’s project.

Metagenomic Protein Discovery: For projects seeking a particular function or enzyme activity, but without a precisely defined sequence, Ginkgo offers a large in-house discovery library of more than 2 billion genes. This library is substantially larger than public repositories and enables the discovery of previously undescribed functional proteins and enzymes.

ML-Guided Protein Engineering: Enzyme Intelligence™ is Ginkgo’s platform for protein engineering employing generative AI and structure-based design. Our protein engineering team is distinguished by the depth of their experience, having delivered dozens of projects across a range of applications, and the large datasets they can access through Ginkgo’s experimental and assay capabilities.

Industry-Leading Automation: Ginkgo has invested almost half a billion dollars in foundry infrastructure, including an expansive robotics platform for automated DNA assembly, transformation, and strain characterization. Data-rich enzyme engineering projects are needed to make the most of data-hungry ML software. High-throughput strategies that can discover rare high-performance variants that can be missed with low-throughput approaches.

Phenotypic Selection with EncapS: The EncapS (Encapsulation and Screening) system allows up to one million strain variants to be characterized in a single campaign. The ultra-high-throughput technology uses microfluidics to package cells in nanoliter-scale droplets, allowing measurement and optimization of secreted protein production. As a screening technique, EncapS can enable strain improvement even without targeted genetic modifications.

Experience Matters: Success-Based Pricing

The depth of Ginkgo’s experience in protein and enzyme production projects gives us a unique confidence in our ability to meet our customers’ performance targets. Alyssa Blaize, Director of Growth, presented our new Success-Based Pricing model as a way for Ginkgo to “put our money where our mouth is” and to allow our customers to directly benefit from that experience.

Projects that are covered by Success-Based Pricing include enzyme discovery, protein engineering and production optimization projects that are determined to have a high probability of success. Ginkgo and our partner work together to set the performance targets for a particular project. If the performance targets aren’t met, the customer pays no R&D fees.

This presentation included more details about the Success-Based Pricing model and a project flowchart highlighting decision points and cost structures at each phase. With Success-Based Pricing, customers are able to lower their technical risk and minimize their financial exposure to the traditional uncertainties of biology R&D.

Gene Therapy Services at Ginkgo

Posted on by Ginkgo Bioworks

James Smith, PhD, Senior Mammalian Engineer  shares an overview of how Ginkgo’s services can help those innovating in gene therapies for greater efficacy, specificity, and manufacturability. 

Watch the full presentation here or read below for a summary.

Advances in synthetic biology are changing the way diseases are treated

That’s why, for the past four years, we’ve built out our platform capabilities for therapeutics.

Synthetic biology is transforming lives through AAV therapy

Jack Hogan, who had hereditary blindness, received a single AAV treatment to deliver the corrected form of a gene. He was able to ride his bike at night within three weeks. Synthetic biology has the potential to improve and transform lives, one person at a time.

At Ginkgo, our mission is to make biology easier to engineer, so we can help companies improve the efficacy, safety, and accessibility of these medicines.

Tap into our AAV engineering capabilities

With our acquisition of StrideBio, we now have access to an unprecedented depth of data around the structure function relationship of the AAV capsid. The addition of StrideBio’s structure-guided AAV engineering assets combined with our already extensive high-throughput screening capabilities will allow Ginkgo to elevate capsid structural and functional engineering.

Ginkgo Gene Therapy Services

We are a unique one-stop shop, capable of providing R&D services for gene therapy manufacturing across capsid, payload, and cell line optimization. We believe we have the potential to revolutionize gene therapy space by overcoming the challenges associated with pre-existing immunity, tissue tropism, and manufacturability.

Where we stand out

De-risk clinical development:

  • Our libraries are evolved through multiple animal species via a cross-species method. This is to enrich for cross-species compatibility, and can help de-risk clinical development.

Access three tiers of capsids:

  • Our capsids (from our StrideBio acquisition) are currently divided into three tiers of development. 
    • Tier one includes fully developed capsids with extensive data.
    • Tier two capsids have entered the first stages of testing in mice and in vitro models and have demonstrated differentiated profiles.
    • Tier three is made up of capsid libraries and pre-existing evolutionary tissues from StrideBio’s programs. These are ready to deploy for new targets, mine for promising capsid candidates, and to feed Ginkgo’s future capsid engineering.

Refine existing capsids with our unprecedented depth of data:

  • With the acquisition of Stride Bio, we now have access to an unprecedented depth of data around the structure function relationship of the AAV capsid.
  • Our institutional capacity for machine learning and automated high throughput screening will allow us to pursue and build upon the assets from StrideBio.

Leverage our services across all stages of the drug development pipeline

Our world-class synthetic biology platform combines computational design and ultra high throughput genetic engineering and screening. That’s paired with our expertise in process development and manufacturing scale-up.

  • Engineer viral capsids to develop gene therapies with enhanced tropism, reduced immunogenicity, and improved transduction efficiency
  • Engineer payloads with custom regulatory elements and inverted terminal repeats (ITRs) to improve efficiency and efficacy
  • Design and optimize more productive cell lines and processes for efficient gene therapy production

Ginkgo helps your R&D team develop more effective therapeutics and solve your greatest drug development challenges.

Find out more about our biopharmaceutical services today!

What will you grow with Ginkgo?

Enhancing Premium Distilled Alcoholic Beverages with Voodoo Scientific

Posted on by Jennifer Wipf

Today, we’re announcing our new partnership with Voodoo Scientific!

Voodoo plans to leverage Ginkgo Enzyme Services to help produce a component of ultra-premium spirit products that are truly smooth.

Most distilled alcoholic beverages produce some degree of harsh sensation, or “bite,” when consumed, which is a major deterrent for many potential customers. Voodoo identified the scientific cause for this harshness and created an enzymatic solution to give distillers the ability to manage it. Distillers can use Voodoo’s novel enzymatic solution to produce more premium products by creating smooth spirits.

Our extensive protein discovery and design capabilities will be used to help develop and optimize the enzyme critical to Voodoo’s product for a wide range of conditions in spirits manufacturing, from craft to global-scale production environments.

“Providing distillers with a means to eliminate, or control, the harshness of their spirits products is very gratifying,” said Joana Montenegro, co-founder and Chief Science Officer at Voodoo. “We believe we can enable new innovation in this large global industry and in ways that are truly meaningful to consumers seeking premium experiences. Ginkgo was the best choice of partners for us among the ones we considered because of their unique combination of strong scientific capabilities and a business model that fits an early-stage company like ours.”

Engineering this class of enzyme to operate under the unique conditions required for distilled alcoholic beverages is a great application for Ginkgo Enzyme Services. Improving the functionality of enzymes underpinning critical production processes – making enzymes work better – is an area we’re passionate about because it opens up real business opportunities for our customers, especially as they push into new product development.

To learn more about Ginkgo’s work in this space, join us on June 30th from 10:00 – 11:00 am ET for our Functional Food Proteins with Microbial Expression Systems virtual event.

What will you grow with Ginkgo?

Enzyme Discovery and Engineering at Foundry Scale

Posted on by Ginkgo Bioworks

Ginkgo Ferment 2023, Platform Presentation:

Ginkgo’s Head of Protein Engineering, Emily Wrenbeck, PhD, shares how our foundry makes it possible to generate valuable data that drives enzyme discovery and optimization.

Watch the full presentation here or read below for a summary.

At Ginkgo, we understand the value of data in biological engineering.

We source natural libraries of proteins through public and proprietary sequence databases. And we’ve built a broad computational protein design toolkit that includes classic methods like molecular dynamics and Rosetta. We also use the latest AI models for protein predictions, including AlphaFold and EVcouplings. Our Protein Production Services allow us to take a supervised machine learning approach to protein design, which means we train models directly on the experimental data that we generate in the process.

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What does all of this look like in practice? Here’s an example: 

  • A customer asked Ginkgo to optimize an enzyme that was critical to their project. The challenge? The enzyme was known to be difficult to engineer, due to its recalcitrant nature and unsolved reaction mechanism. In this case, traditional rational protein engineering approaches were not feasible.
  • To tackle this problem, Ginkgo opted for a data-driven approach to protein design. We engaged in four rounds of Design, Build, Test, and Learn. In the early rounds, we used a design toolkit with sequence-based, self-supervised model active sign mutagenesis and Rosetta docking to explore the sequence to activity relationship of the protein.
  • In the successive rounds, we fed all the data into our platform to train models and build designs. The library sizes in the final round were able to realize a big leap in performance with a rather small library. As the models are given more data, they get more predictive, enabling us to hit our goals in a much more focused way.
  • The outcome of this approach was a tenfold improvement over the starting enzyme. Our data-driven approach proved to be effective, even for a challenging enzyme that was not amenable to traditional protein engineering techniques.

This case study highlights the importance of how data enables breakthroughs in biological engineering. It also shows the power of a platform approach that combines state-of-the-art AI and computational tools with a data generation engine.

By investing in data generation and computational tools, we can push the boundaries of what is possible in protein design and engineering.

We’d love to add your enzyme to our growing list and help design and engineer it to fit your needs. Learn more about our Ginkgo Enzyme Services today!

What will you grow with Ginkgo?

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