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

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.

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

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

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

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

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

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

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.

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?

AgBiome Leverages Ginkgo Strain Optimization Services

Today we’re announcing a partnership with AgBiome, a leader in global microbial innovation.

The aim is to optimize the performance of products in AgBiome’s pipeline of agricultural biologicals. Organizations developing next generation agricultural inputs can access our platform to accelerate discovery and deployment of new products.

By leveraging Ginkgo’s Strain Optimization Services, AgBiome aims to provide growers with new and improved live microbial strain products.

The biological crop protection market has significantly grown in recent years. Growers have increasingly sought effective and sustainable alternatives to synthetic pest control products. By leveraging our suite of advanced biology tools, AgBiome aims to enhance the breadth and efficacy of novel biological products.

We believe we can identify improved variants at massive scale.

That can help deliver more potent agricultural biologicals and bring the next generation of products to market. We are thrilled to work with an industry leader like AgBiome as we seek to optimize live microbial strain products in their pipeline and provide even better solutions to growers around the world.

“AgBiome is committed to creating the most effective crop protection products, and we are always looking for new technologies to enable better performance. We are excited to utilize Ginkgo’s capabilities in ultra high throughput assay development to evolve the next generation of biologicals as we continue to provide growers with improved product efficacy.”

-Scott Uknes, Co-founder and Co-CEO of AgBiome

Ginkgo’s ultra high throughput encapsulated screening technology:

  • Makes it possible to search through up to 1 million strain variants in a single run
  • Selects the best performing candidates for further development
  • Is built on nanoliter encapsulation technology, and thus provides nanoscale growth and assay compartments
  • Makes it possible to greatly reduce the screening time for large libraries

 

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

What will you grow with Ginkgo?

Virtual Event: Cell Therapy Services

Watch the Event

On May 31st, Ginkgo hosted a live webinar to present our capabilities and latest results in CAR-T engineering and cell therapy.
A recording of the Virtual Event, Cell Therapy Services, is available here.

A Platform of Platforms for Full-Stack Engineering

Shawdee Eshghi, Senior Director of Mammalian Engineering, shared an overview of Ginkgo’s platform for mammalian cell engineering for biopharmaceutical applications. Advances in synthetic biology are revolutionizing medicine across a range of modalities and disease areas. By making biology easier to engineer, Ginkgo can help our customers improve efficacy, safety and access to these remarkable medicines.

For cell therapeutics, Ginkgo offers services in three categories, all supported by our industry-leading platform for DNA assembly, agile automation, and high-throughput screening in clinically relevant assays.

  • Novel CAR Designs. Ginkgo has constructed libraries of novel ICDs, ECDs and armoring domains to optimize your CAR’s performance. We can perform pooled CAR screening in primary immune cells, offering both off-the-shelf assays and bespoke application-specific assays.
  • Regulatory Elements. Tissue-specific promoters can improve the efficacy or the safety profile of your cell therapy. Strong and stable expression elements can increase potency. Ginkgo can assemble and screen large libraries of custom regulatory sequences.
  • iPSC Engineering. Ginkgo’s platform can support the development of allogeneic cell therapies as well as more predictive in vitro models. We have extensive experience working with iPSCs coupled by our enabling platform technologies that include promoter screening, safe harbor discovery, directed differentiation optimization, and improved immune evasion strategies.

Combinatorial CAR Engineering at Scale

Taeyoon Kyung, Senior Mammalian Engineer, presented recent results from a foundry project to characterize 10,000 CAR intracellular domains (ICDs). Ginkgo identified multiple designs that outperformed standard CD28-CD3z and 41BB-CD3z designs in a serial tumor rechallenge model for T cell persistence. A range of follow-up assays were presented to characterize CAR4, a high performance design with improved proliferation, killing, and long-term fitness in challenging contexts.

This combinatorial CAR library screen demonstrates the potential of Ginkgo’s automation and design capabilities to deliver best-in-class cell therapeutics across a range of applications. The libraries developed for this project have been screened against suspension, adherent and spheroid target cells. A similar approach can be brought to bear to optimize CAR extracellular and intracellular domains in parallel in any given immune cell type. High throughput DNA synthesis and library assembly can support your R&D efforts across a range of therapeutically relevant synthetic proteins.

What Can Ginkgo’s Cell Therapy Services Do for You?

Ginkgo’s service offerings are well positioned to help R&D teams address a number of common challenges in creating an effective cell therapy: T-cell exhaustion, immunosuppression in the tumor microenvironment, antigen escape, cytokine toxicity.

For customers interested in our cell therapy offerings, we offer a range of partnership structures tailored to the scope and needs of your project. A direct evaluation and licensing model is available to put Ginkgo-built tech in your hands today. Alternatively, we can enter into an R&D collaboration to design, build, screen and optimize a cell-based therapeutic specific to your application. Your team will then have the option to evaluate and license the final designs. We look forward to working with you!

Sustainable Innovation in Generic API Space with Centrient

Reducing the Environmental Footprint of Enzymatic Production of APIs

Today we’re pleased to announce an expansion of our existing partnership with Centrient, the global business-to-business leader in sustainable antibiotics, next-generation statins and anti-fungals. The partnership is aimed at broadening Centrient’s portfolio of environmentally friendly active pharmaceutical ingredients (APIs), following the success of previous work together.

Our ongoing partnership with Centrient focuses on improving the sustainability of fermentation and enzymatic syntheses of beta-lactam antibiotic APIs. In the first phase of this project, we delivered an enzyme with significantly improved efficiency, reducing the environmental footprint of enzymatic production of amoxicillin and cephalexin APIs. These semi-synthetic beta-lactam antibiotics are widely prescribed to both children and adults and are on the World Health Organization’s List of Essential Medicines. Centrient aims to build on these improvements through ongoing strain projects on our platform which focus on reducing carbon emissions and waste production compared to traditional chemical routes.

Our Ginkgo Enzyme Services are enabling Centrient’s sustainable API production

“Our partnership with Ginkgo is fully aligned with our main purpose: to improve lives through innovative and sustainable manufacturing of medicines,” said Jorge Gil-Martinez, Chief Scientific Officer at Centrient. “The initial success of this collaboration has led us to expand our joint efforts to design new ways of producing essential medicines, minimizing the environmental impact of antibiotic manufacturing. Moreover, as we design and execute our Open Innovation business model, this strategic collaboration creates synergies to accelerate the diversification of our portfolio, a strategic pillar for the future of our company. Access to external disruptive technologies, focusing on enzymes and fermentation, contributes to our vision to be a diversified and integrated partner of choice for generic medicines.”

Our partnership with Centrient, which began in 2021, underscores Ginkgo’s commitment to supporting biopharma companies in bringing much-needed innovation to the field. We are inspired by the early success we’ve already seen in our partnership and look forward to expanding our joint efforts to ultimately support better patient outcomes.

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

What will you grow with Ginkgo?