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!

Novel Therapies for Hard-To-Treat Diseases with Boehringer Ingelheim

Today we’re pleased to announce a new partnership with Boehringer Ingelheim!

Through this partnership, Boehringer Ingelheim will leverage our natural product discovery capabilities. The goal is to accelerate their discovery and development of novel therapeutic molecules to address diseases with high unmet patient needs.

Hundreds of millions of people are living with diseases that to date cannot be cured or are inadequately treated. Breaking through this inertia requires, in many cases, the use of new techniques to act on molecular targets which are exceedingly difficult to address with traditional approaches.

Boehringer Ingelheim will utilize our  metagenomic sequence database. This provides access to a vast reservoir of structurally novel bioactive molecules.This access can potentially enable the rapid identification of lead molecules as starting points for the potential discovery of novel treatments to transform patients’ lives.

Unlocking new possibilities in biopharma innovation

We are well-positioned to help partners like Boehringer Ingelheim complement their drug discovery efforts, particularly when it comes to natural product discovery.

We’ve built one of the broadest and deepest metagenomics databases worldwide, aided by our recent acquisition of Zymergen. The database comprises over three terabases of sequence data and over two billion proprietary protein sequences from a variety of microbes. This creates a unique foundation for the discovery of novel therapeutic molecules.

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

What will you grow with Ginkgo?

Upcoming Presentation at American Society of Gene & Cell Therapy

Today we are pleased to announce our participation in the 26th American Society of Gene & Cell Therapy (ASGCT) Annual Meeting, May 16-20, in Los Angeles.

We will present data on our high-throughput screening platform for chimeric antigen receptor (CAR) libraries, which can enable discovery of CAR variants with desired characteristics. This capability has the potential to discover CAR-T therapeutic candidates that are effective against solid tumors.

We are harnessing our ability to generate massive libraries of unique CAR designs with different signaling domains, which can then be screened in an assay that mimics a solid tumor environment. In head-to-head tests of these designs, we are identifying a number of designs that show improved performance compared to designs with standard signaling domains.

We’re excited to present this data to the ASGCT community, especially as this flexible platform is available to partners and can also be used for other applications like natural killer cells.

We recently announced the launch of Ginkgo Cell Therapy Services at our annual Ferment conference.

These services empower customers with massively parallel testing of genetic designs, allowing them to leverage vast biological diversity to improve their products. Our ultra high throughput mammalian cell engineering foundry is well suited to address many outstanding problems in cell therapy, including CAR-T. We are actively developing high throughput platforms to enhance CAR efficacy and safety by exploring novel construct designs and incorporating synthetic regulatory elements like inducible promoters. In addition to CAR optimization, Cell Therapy Services include immune cell armoring, synthetic promoters, immune cloaking and novel gene editing tools.

You can learn more at Ginkgo’s Cell Therapy Services Virtual Event on May 31. Register here.

What will you grow with Ginkgo?

Developing a Novel mRNA Manufacturing Platform with Sensible Biotechnologies

An in vivo alternative to conventional in vitro mRNA production technology

Today, we are pleased to announce our partnership with Sensible Biotechnologies to develop an in vivo microbial mRNA manufacturing platform. Currently, the vast majority of mRNA used in vaccines, therapeutics and other applications is produced by in vitro transcription (IVT), a cell-free process, which is driven by purified enzymes. In conventional mRNA manufacturing, production runs are typically limited in reaction volume size, and the resulting mRNA needs to go through expensive purification processes to eliminate potentially harmful byproducts like dsRNA, which can cause adverse immune responses in patients. Moreover, it is difficult to produce high yields of certain kinds of mRNA in an IVT reaction. By contrast, the in vivo mRNA manufacturing method that we are working to develop with Sensible is designed to scale upwards of 100,000L. The ultimate goal is to use  superior quality mRNA over traditional IVT- allowing for the production of mRNA molecules with increased length – and to expand the potential of the mRNA platform to novel therapeutic modalities.

Enabling the advent of novel mRNA medicines

“mRNA technology has a potential to bring many life-saving therapeutics and vaccines, but its current, cell-free production represents one of the major bottlenecks. In vivo mRNA manufacturing could enable scalable mRNA manufacturing, which has long relied on production methods that face quality control challenges and are inherently difficult to scale,” said Miroslav Gasparek, CEO at Sensible. “By working with Ginkgo, we aim to create a scalable commercial-grade manufacturing platform that produces mRNA of higher quality than is possible through in vitro expression and enable the advent of novel mRNA medicines.”

As the market for mRNA continues to expand, biopharma companies are looking for more efficient and scalable production platforms to produce high-quality mRNA. As we deepen our commitment to the emerging field of nucleic acid therapeutics, we are excited to work with the team at Sensible to optimize their microbial mRNA production platform with the goal of unleashing a new generation of mRNA products.

This partnership builds on our existing pipeline of mRNA-related programs, Including our work with Moderna to support process optimization for raw materials used to make mRNA vaccines. Furthermore, through our partnership with Aldevron, we optimized the production of vaccinia capping enzyme, an important component often required to manufacture mRNA vaccines and therapeutics. Most recently, we announced the acquisition of Circularis, a biotechnology company with a proprietary circular RNA and promoter screening platform, and is actively engaged in improving circular RNA efficacy and manufacturing yields.

To learn more about Ginkgo Enzyme Services, 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?

Optimizing Enzyme Expression and Performance with Zymtronix

Optimizing enzymes for Zymtronix’s cell-free manufacturing platform

Today we are pleased to announce our partnership with Zymtronix, a developer of cell-free process technologies. Together we aim to optimize enzymes used in Zymtronix’s proprietary cell-free platform for the production of important ingredients in food, agriculture, cosmetics and pharmaceuticals.

Enzymatic biocatalysis is a powerful manufacturing technology that can enable the production of a wide range of chemicals and molecules. Zymtronix’s cell-free platform is designed to solve challenges associated with traditional biocatalysis and seeks to enable the production of a wide range of products with precision and productivity. By partnering with us to build and produce bioengineered market-ready enzymes, Zymtronix anticipates being able to extend its solutions into the pharma, nutrition, agriculture markets, among others.

Zymtronix aims to leverage Ginkgo Enzyme Services to discover, optimize, and produce enzymes

Ginkgo Enzyme Services offers partners end-to-end support for the discovery, optimization, and production of enzymes for diverse applications. Through the partnership, we will leverage our suite of enzyme services to engineer enzymes for Zymtronix’s applications using metagenomic enzyme discovery as well as improve enzyme expression and production host performance.

We’re thrilled to welcome Zymtronix to the platform and support their applications in sustainable ingredients and beyond. We’ve built out our platform to serve a wide variety of enzyme discovery, engineering, optimization and scale up efforts, and we’re so excited for the work to come in this partnership. Zymtronix’s cell-free biomanufacturing platform is pioneering solutions for various industries, and we’re eager to leverage our end-to-end capabilities and help expand its efforts in transforming the way enzymes are used.

“This partnership will greatly accelerate our work of bringing the precision and scalability of cell-free biomanufacturing and sustainable ingredients to market starting with alternatives to animal sources; Ginkgo is uniquely able to support us with both enzyme engineering and strain expression, helping us continue to accelerate commercialization,” said Stéphane Corgié, CEO-CTO and founder, Zymtronix. “We hope to extend this partnership in the future to facilitate the production of multiple end-market products.”

To learn more about Ginkgo Enzyme Services, 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?

Engineering Bacteria for Cancer Patient Treatment with Prokarium

Partnership with Prokarium to discover multiple targets for RNA therapeutics and immuno-oncology

Today, we’re announcing a new partnership with Prokarium – a biopharmaceutical company pioneering the oncology field of microbial immunotherapy – to develop a bactofection platform to deliver RNA-based therapeutics.

Most gene therapies today use viral delivery systems, which may have limited utility due to toxicity and targeting issues. Bactofection, the process of transferring genetic material into a mammalian cell via a bacterium, is an alternative gene delivery system that could deliver therapeutic agents to a patient. In bactofection, the naturally occurring tumor-colonizing characteristics of bacterial species, such as Salmonella, can be modified via genetic manipulation and harnessed to be a targeted delivery vehicle for various therapeutic payloads.

Developing bactofection platform to treat cancer patients

In collaboration with Prokarium, Ginkgo will set out to engineer a Salmonella-based bactofection platform for the delivery of RNA payloads to treat cancer patients, building on existing capabilities in RNA therapeutics, viral-based gene therapy and bacterial therapeutics.

“By leveraging Ginkgo’s microbial and mammalian foundry capabilities, we are building a highly versatile and innovative bactofection platform to support delivery of novel modalities from the ground up,” said Kristen Albright, CEO at Prokarium. “Through this partnership, we are working to unlock a new generation of immuno-oncology therapeutics.”

Advancements in immunotherapy such as checkpoint inhibitors and CAR-T have transformed the treatment of certain cancers, with tremendous progress across novel modalities continuing to build. With Prokarium, we will work to develop a bactofection platform that leverages the convergence of these advancements in immuno-oncology, gene therapy, RNA therapeutics and bacterial therapeutics. We are  excited to bolster our work with leading companies like Prokarium, which can utilize our services to innovate and expand what is possible with novel therapeutics.

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

What will you grow with Ginkgo?

Developing Circular RNA-based Therapeutics with Esperovax

Initial focus of partnership will aim to develop cancer therapeutics

Today, we announced a partnership with Esperovax, an innovative developer of oral mRNA biologics, to develop circular RNAs (circRNAs) for a variety of therapeutic applications. Initially, Ginkgo and Esperovax will work to develop circRNAs harboring payloads to specifically target colorectal cancer by inducing cell death only in cancerous cells.

CircRNAs represent an emerging, powerful mechanism for delivering therapeutics and vaccines due to their protein-coding potential and improved stability in comparison to their linear mRNA counterparts.

This partnership aims to further exploit circRNAs by developing a novel mechanism to facilitate RNA circularization specifically in colorectal cancer cells. This would result in extended expression of the toxic payload solely in cancer cells, reducing toxicity and resulting side effects from the death of normal cells. By combining omics datasets, computational approaches, and high-throughput screening capabilities, Ginkgo will design, build and screen large numbers of RNA designs that leverage and optimize Esperovax’s novel mechanism of cell-type specific circularization.

Through our growing portfolio of programs in cell and gene therapy and RNA therapeutics, and recent acquisition of Circularis, Ginkgo is uniquely positioned to enable new solutions in these areas with circRNA.

“Given therapeutic developments in recent years, the idea of inducing a suicide gene therapy system in a tissue-specific manner has gained traction,” said Randy Wayne Schekman, a Nobel Prize recipient in Physiology or Medicine and Advisor at Esperovax. “As we aim to build off that traction with the ultimate goal of improving cancer patient outcomes, Ginkgo’s momentum and achievements in the therapeutics space made the company an essential and trusted team to partner with, giving us the confidence that we can eventually make this goal a reality.”

We’re thrilled to use our platform to further develop and optimize Esperovax’s novel mechanism for circularization and enable advancements in the therapeutics space – a core area of our work together.

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

What will you grow with Ginkgo?

High Throughput Screening for Designing Novel CAR-T Cell Therapies

Pooled screening platform for discovering the next generation of CARs

Image of a poster containing CAR-T data

Ginkgo is proud to present a poster this Friday, November 11 at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC). The poster highlights our Foundry-enabled methods for large-scale, combinatorial library design and screening of chimeric antigen receptor (CAR) domains for improved persistence. The ability to screen hundreds of thousands of CAR designs in primary human T cells can enable discovery of variants with desired characteristics. This capability has the potential to discover CAR-T therapies that are effective against solid tumors.

CAR-T cell therapies show tremendous promise for the treatment of cancer. But so far, their use has been limited to targeting blood cancers, as CAR-T has failed to show consistent efficacy in treating solid tumors, which represent approximately 90% of adult human cancers. Part of the challenge when applying CAR-T therapies to solid tumors lies in T cell exhaustion, a state of dysfunction arising from excessive antigen stimulation in the immunosuppressive environment of a solid tumor.

Therapeutic outcomes of CAR-T cell therapies—including CAR-T persistence—correspond to T cell behaviors driven by signaling cascades that are triggered by the intracellular domains (ICD) of CARs. Until now, technical constraints in high throughput screening have made the systematic design and testing of novel ICD combinations that drive more favorable T cell phenotypes onerous. New data we are presenting at SITC will demonstrate that our high throughput screening method enables massively parallel testing of CAR designs and has led to the discovery of new ICD combinations that outperform the canonical CD28-CD3z and 4-1BB-CD3z combinations.

Discovering next generation CAR-T cell therapies

Our platform for cell programming enables synthesis and screening of diverse libraries of genetic constructs to explore biological space. Applying these capabilities to the design of CARs enables screening of hundreds of thousands of possible combinatorial variants of different CAR ICDs. The data we will present at SITC will show how this method could be used to screen for variants with increased persistence in a serial tumor rechallenge assay. As an enabling platform company, we can leverage our full stack of mammalian cell engineering expertise and capabilities to enable the high throughput screening of CAR-T cells to discover and optimize next generation therapeutic candidates for our partners.

While innovation in CAR-T cell therapies continues to grow at a dramatic pace, CAR-T is still a relatively new modality whose potential is just beginning to be fully explored. With large scale screening and automation, we have created a tool we believe can dramatically expand the variety and functionality of CAR domains so that our partners can build therapies targeted for particular tumor environments.

“We’ve only seen a small sliver of what revolutionary modalities like CAR-T can achieve in terms of patient outcomes. Being able to explore broader design space for this powerful technology can help unlock new potential in solid tumor treatment, inflammatory and autoimmune diseases, and beyond.” said Arie Belldegrun, Executive Chairman and Co-Founder of Allogene Therapeutics and Kite Therapeutics and member of the Board of Directors for Ginkgo Bioworks. “The scale of Ginkgo’s platform helps to enable discovery and innovation in this important arena.”

You can view our poster at SITC. To register, visit www.sitcancer.org/2022.

Presentation details:

Date & Time: Friday, November 11, 2022 at 9 am – 8:30 pm, EST
Title: Pooled screening platform for discovering the next generation Chimeric Antigen Receptors
Presenting Author: Taeyoon Kyung, PhD, Senior Mammalian Engineer, Ginkgo Bioworks
Poster Number: 242

Click here to speak with our team and learn more about leveraging our platform.

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

What will you grow with Ginkgo?

Optimizing Crucial Drug Manufacturing of APIs with Merck

Ginkgo to engineer key biocatalytic enzymes for potential use in Merck’s drug manufacturing processes

Today, Ginkgo is proud to announce a collaboration with Merck to optimize the manufacture of active pharmaceutical ingredients. The aim is to engineer up to four enzymes for use as biocatalysts in Merck’s active pharmaceutical ingredient (API) manufacturing efforts. Through this collaboration, we will leverage our extensive experience in cell engineering and enzyme design, along with our capabilities in automated high throughput screening, manufacturing process development/optimization, bioinformatics and analytics to deliver optimal strains for expression of targeted biocatalysts.

Biocatalysis is a sustainable and effective alternative to some steps in industrial chemical synthesis

Enzyme biocatalysts can reduce costly synthesis and purification steps, thereby decreasing production costs. Through this collaboration, we aim to optimize several biocatalysts by leveraging our world-class proprietary fungal strains, cell line development, enzyme engineering and optimization, and multiomics expertise.

“Ginkgo’s fungal strains present a major opportunity for improving biocatalysis. E. coli is currently the mainstay host for expressing enzymes, but a large number of enzymes will not express properly in E. coli, and those that do express in E. coli may have better homologs that only express in fungal strains,” said Behzad Mahdavi, our Senior Vice President of Biopharma Manufacturing and Life Sciences Tools. “This enzyme optimization project with Merck has the potential to help reduce the cost of goods and enable a more robust supply chain for APIs.”

Merck is a pioneer in biocatalysis, improving manufacturing of crucial medicines. We’re thrilled to be partnering with Merck and to be leveraging our platform capabilities for improved enzyme activity and production. Ginkgo’s platform model enables us to identify improved enzymes and develop powerful fungal strains and fermentation processes for enzyme manufacturing, empowering downstream API production for our customers.

Under the terms of the collaboration, Ginkgo will earn an upfront research and development fee and is eligible for success-based research and development milestone payments. In addition, Ginkgo is eligible to earn commercial milestone payments for each of a specified number of biocatalysis targets, which have the potential to total, in the aggregate, up to $144 million. To learn more about Ginkgo’s work in enzyme discovery, visit this webpage and talk to our team today.

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

What will you grow with Ginkgo?

Developing Synthetic Biotics for Gout with Synlogic

Ginkgo and Synlogic announce the second drug candidate—a treatment for gout—in their partnership to develop synthetic biotics

Last November, we announced that SYNB1353, an engineered strain of the probiotic bacteria E. coli Nissle (EcN) designed and developed through a collaboration between Ginkgo and Synlogic, was to be nominated for investigational new drug (IND) status with the U.S. Food and Drug Administration (FDA). This would mark the first medicine developed on Ginkgo’s platform to enter IND-enabling studies but just the beginning of our work with Synlogic to create living medicines.

Today, we’re pleased to share Synlogic’s announcement of SYNB2081, a new drug candidate developed in partnership between our two companies for the treatment of gout.

Addressing unmet needs for patient care

Gout is a complex form of inflammatory arthritis that occurs when excess uric acid in the body forms crystals in the joints. Patients experience a range of symptoms, including intense joint pain, inflammation and redness, and limited range of motion in the affected joints. Unfortunately, current treatment options present limitations in both safety and efficacy, highlighting a need for new approaches.Gout is also a recognized risk factor in chronic kidney disease (CKD).

SYNB2081 is a synthetic biotic designed to lower uric acid for the treatment of gout. We’re honored to work with the Synlogic team in this pioneering next step to potentially help patients living with gout. As we’ve seen the Synlogic pipeline develop the past year, we’re eager to continue supporting Synlogic in generating additional therapeutic candidates.

SYNB2081 is named after one of the largest and best-preserved Tyrannosaurus rex specimens in the world. Nicknamed “Sue,” the specimen is housed at the Field Museum in Chicago and is officially named FMNH PR 2081. Data from “Sue” suggests that dinosaurs like the Tyrannosaurus rex suffered from gout much in the same way as other reptiles and birds do.

What if we could program microbes to act as medicine?

“With our second drug candidate into clinical development, this not only demonstrates the value of combining Ginkgo’s Codebase with our Synthetic Biotic platform, but also highlights the potential to develop Synthetic Biotics across a range of diseases, giving us the potential to provide meaningful new treatment options to patients in need,” said Dr. David Hava, Chief Scientific Officer, Synlogic.

The advancement of SYNB2081 and SYNB1353 are clear indicators of the transformative platform Synlogic has created to power new medicines through synthetic biology.

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

What will you grow with Ginkgo?