Ginkgo Ferment 2023, Platform Presentation on Cell Therapy Services:

Shawdee Eshghi, PhD, Senior Director of Mammalian Engineering shares an overview of Ginkgo’s ability to help customers program new medicines. Our services represent a significant step forward in the development of cancer treatments and we believe we can increase CAR-T’s effectiveness due to our large-scale testing capabilities and ability to read and write DNA.

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

Synthetic biology can transform lives:

The CAR-T revolution enabled a toddler named Emily Whitehead, who had failed multiple lines of therapy, to receive reprogrammed cells that attacked her cancer. Emily is now thriving as a teenager and living the life every parent wants for their child. This remarkable demonstration is why we at Ginkgo are dedicated to helping companies increase the effectiveness of CAR-Ts.

At Ginkgo, we’ve created 10,000 unique CAR-T designs using large DNA libraries and cost-effective sequencing — all differing in their inside signaling parts. We insert these designs into T-cells and test them in an assay which mimics solid tumors. Each design has a DNA barcode, which enables us to use our sequencing capability to read the effects of all 10,000 designs. A head-to-head comparison with existing FDA designs shows that our designs are meaningfully better.

Dramatically expand the variety and functionality of CAR domains:

Our partners can discover and optimize next generation therapeutic candidates by leveraging our full stack of mammalian cell engineering expertise and capabilities that enables high throughput screening of CAR-T cells.

In a typical Ginkgo experiment, we can:

• Combine 10,000 different signaling domains with various CAR binders of different affinities
• Test them in T-cells from different donors against multiple tumor cell lines with a high replication factor
• Run 720,000 unique tests in one experiment, which allows our team to significantly improve the function of the CAR-T therapies

What our full stack of mammalian cell engineering expertise and capabilities can do for you:

• Design and screen large pooled combinatorial libraries of CAR domains to find the most effective design for improved persistence
• Develop and optimize synthetic inducible promoters for expression and targeting of CAR therapies
• Optimize construction of CAR-T, CAR-NK, and other cell types with iPSC genomic safe harbors
• Use our platform to reduce the screening process to practice. Partners can simply repeat the process and obtain new results within a short period of time.

Future modalities of CAR-T:

We’ve built a suite of services that not only address autologous CAR-T, but also the future modalities of CAR-T, including allogeneic treatments.

We are also mining for novel gene editors from our proprietary metagenomic databases. We then screen them in relevant cell types, while taking a new approach to immune cloaking. This involves hiding transplanted cells from the immune system to prolong their function.

Ginkgo’s services can help 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?

On May 10 we hosted a webinar to present Ginkgo’s AAV services for gene therapy.

These services address the most significant challenges in AAV gene therapy: tissue tropism, potency, neutralizing antibodies, cross-species translatability, manufacturability, and COGS. The event featured presentations from our team describing our current capabilities in three domains.

• Capsid Engineering. Ginkgo can engineer AAV capsids to enhance potency, reduce off-target and neutralizing antibody binding, improve manufacturability, and improve tissue tropism and cell-type specificity.

• Payload Engineering. High-performance therapeutics benefit from fine-tuned promoters, tissue-specific regulatory elements, and engineered structural elements like ITRs. Ginkgo can explore large sequence design spaces and characterize performance with pooled screening, including directly in animal models.

• AAV Manufacturability. For gene therapies to reach patients, they need to be manufactured at scale. Ginkgo can improve your gene therapies’ manufacturability with high expression production vectors, high performance cell lines, or by bringing our gene editing tools to the production cell lines that you already use.

The STRIVE Platform Comes to the Foundry

In April of 2023, Ginkgo announced the acquisition of StrideBio. StrideBio’s STRIVE platform includes a set of mature and validated AAV capsids with extensive testing in large animal models. Data for two of these AAV capsids were presented during the event.

• STRV 5 targets the tissues of the CNS. It has been extensively vetted for its biodistribution and expression in mice, pigs, and NHPs. It was selected for its cell-type specificity, liver de-targeting character, and manufacturability.
• STRV47 is a pan-tropic capsid with enhanced potency. It was developed through cross-species evolution in Pigs, Mice, and NHPs and enrichment of AAV sequences found across the brain and spinal cord.

The variants of these capsids similarly exhibit a wide range of diversity in their tissue tropism, with capsids targeted to the CNS, heart, muscle, liver, lungs, and even to T-cells.

In Ginkgo’s Foundry, these proprietary capsid technologies are only the beginning. Our extensive capacity for high-throughput engineering of proteins and regulatory elements can enable the ambitions of our partners across the gene therapy space. The event presented several ways in which Ginkgo’s large datasets and scalable automation can make our partners’ AAV therapeutics easier to engineer.

What can Ginkgo AAV Services do for you?

Ginkgo’s customers can access our capsid offering through either a licensing or a partnership model. Our pre-validated capsids with proven performance in large animal models are immediately available for license.

For customers with more bespoke needs, we offer research collaborations to develop novel capsids tailored to your requirements. Unlock the power of the Foundry to leverage our large capsid libraries, our deep expertise in capsid design, and our extensive automation infrastructure for your R&D projects.

Watch the Event

A recording of the Virtual Event, AAV Services, is available here.

What will you grow with Ginkgo?

Ginkgo Ferment 2023, Platform Presentation on RNA Therapeutics:

Shawdee Eshghi, PhD, Senior Director of Mammalian Engineering shares an overview of how Ginkgo’s services can help those innovating in RNA Therapeutics for greater efficacy, specificity, and manufacturability.

Watch the presentation here or read below for a summary.

Ginkgo is your cell engineering partner

From small molecule discovery and manufacturing to biologics, cell and gene therapy, RNA therapeutics and vaccines, and beyond. Our services help enable discovery, optimization, and scale up for a wide range of therapeutics modalities.

Momentum is building in the clinic for RNA therapeutics

Future clinical care of human diseases will likely include promising RNA therapeutics.

Ginkgo explores untapped biological diversity through ultra high-throughput genetic design, integrated data analytics, and model building. This approach has allowed us to explore different therapeutic modalities, including RNA therapeutics.

Circular RNA technologies

We’re exploring the potential of circular RNA to improve programmability, stability, durability, and other properties. In a recent study, the extended-expression time of different circular RNA designs made at Ginkgo was compared to traditional linear capped mRNA. The results showed that circular RNA has a longer expression time.

Through our recent acquisition of Circularis, Ginkgo is uniquely positioned to enable new solutions in these areas with circRNA. CircRNAs represent an emerging, powerful mechanism for delivering therapeutics and vaccines, in part due to their protein-coding potential and improved stability compared to their linear mRNA counterparts.

We are also developing our own circular RNA platform, which is currently achieving over 80% purity – a high bar for advanced therapeutics.

Novel mRNA technologies

We recently signed a partnership with Sensible Biotechnologies for a novel mRNA manufacturing technology. As we deepen our commitment to the emerging field of nucleic acid therapeutics, we are excited to work with the team at Sensible Biotechnologies to optimize their microbial mRNA production platform with the goal of unleashing a new generation of mRNA products.

We’re thrilled to use our platform to further enable advancements in the therapeutics space – a core area of our work. 

You, too, can leverage our services:

• Utilize proprietary assays and ultra high-throughput screening to optimize the activity and stability of linear and circular RNA for enhanced function and tissue-specific expression and manufacture candidates in quantities ready for animal studies
• Optimize the activity and production of enzyme reagents used in RNA manufacturing and in vitro translation
• Explore the vast sequence space of RNA to optimize RNA translation into proteins and explore how it differs in different cell types and with different payloads
• Increase plasmid titer and optimize downstream processing yield to reduce manufacturing costs

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?

Ginkgo Ferment 2023, Platform Presentation:

Ginkgo’s Head of Agricultural Biologicals, Magalie Guilhabert, PhD covers how innovators can address the challenges growers face in today’s world, leveraging Ginkgo’s platform to discover new biological products and traits and optimize for performance and consistency.

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

Growers face unprecedented challenges. As climate change introduces new stressors, consumer preferences shift, and government regulations change accordingly, growers need to serve larger populations without increasing land under cultivation.

Agricultural technology companies have long looked to biology to develop solutions for growers: from novel plant traits to microbes and microbially-produced active ingredients that deliver crop nutrition and crop protection. These innovators are under pressure to deliver high-performing, consistent, and safe biological products. Their path to commercialization is rife with technical, regulatory, and adoption risk.

Our microbial services can de-risk innovation in three ways:

• Better starting points with wild-type biology

With a microbial library of >200,000 strains, a metagenomic database spanning 5B+ genes and the computational pipeline to screen this data for new active ingredients and traits, Ginkgo aims to provide innovators with better starting points for new products. We believe our discovery services increase the likelihood of finding lead candidates quickly.

• Higher performance with optimization and engineering services

With ultra-high throughput screening capabilities, Ginkgo can unlock the full potential of mutagenesis-led strain optimization. Our rapid strain optimization services can test millions of strains in one campaign for a variety of phenotypes: increased small molecule and protein secretion, enzyme specificity, binding affinity, and growth characteristics under defined conditions. Screening at this scale can help innovators find the needle in the haystack fast, delivering higher performing candidates in less than a year.

Through 15 years of partner-driven and highly automated R&D, Ginkgo has amassed functional data across many protein and pathway designs. We believe this proprietary data enables Ginkgo to intelligently engineer strains and proteins for higher performance. We use machine learning-led protein engineering to curate the set of protein and pathway designs that are most likely to achieve the target outcome. We test these designs in our automated labs, iterating to push the boundaries of performance.

• Improved consistency with formulation and scale-up services

Growers value products that stay stable on the shelf and unleash potent active ingredients once they’re in the field. Confirming consistent performance often requires testing products in the field. To serve this need, Ginkgo’s formulation and scale-up services combine in planta testing, shelf stability studies, and formulation prototyping across a range of product concepts.

Once we’ve validated product performance and stability in growth chambers, micro plots, or greenhouses, we iterate on fermentation process conditions to help achieve cost-effective production. By using our pilot scale facilities, we believe growers will benefit from our fermentation process translating into industrial scale production.

With Ginkgo’s formulation and scale-up services, innovators can mitigate the risk of products failing in the field, during manufacturing, or on the shelf after performing well in the lab.

Find out more about our biologicals services today!

What will you grow with Ginkgo?

On April 26th, we hosted a webinar to discuss Ginkgo’s RNA Therapeutic Services. These services make RNA-based therapeutics and vaccines easier to engineer. The event highlighted our technologies for circular RNA discovery and production that were further augmented by recent acquisition of Circularis, and a full stack of associated services from early-stage to pre-clinical. The event provided an overview of our biopharmaceutical capabilities and how prospective partners can leverage our services to advance their RNA therapeutic development.

Ginkgo’s RNA services

Our RNA services are a comprehensive solution for RNA therapeutic and vaccines R&D, from RNA sequence discovery to production, purification, LNP packaging and binder elements for targeting specific cell types and tissues.

• RNA Sequence Discovery: We can screen large sequence spaces to find functional elements needed in a specific therapeutic context. Customers have access to our library of proprietary and unique IRES sequences for controlling gene expression.
• Circularization: We have proprietary technology for circularizing RNA, which can offer advantages in stability and immunogenicity. We work with a variety of techniques including catalytic introns, hairpin ribozymes, and enzymatic ligation, and can work with linear mRNA as well.
• Production and Purification: We can deliver circRNA at high yield or at high throughput, as your application demands. High-yield capabilities produce RNA at the milligram scale, suitable for larger pre-clinical studies. Our high-throughput-compatible techniques can generate large numbers of RNA molecules at the microgram scale, suitable for pooled in vitro screening.
• Packaging and Delivery: We can screen lipid nanoparticles (LNPs) to identify the right packaging for RNA delivery, or engineer binders, such as antibodies, to help LNPs find the correct cell and tissue types.
• Cell and Tissue Targeting: We can design protein binders, for example antibodies, to target RNA-loaded LNPs to specific cell and tissue types. These capabilities leverage Ginkgo’s established platform for protein design, production and purification.
• Work with us: From small molecule discovery and manufacturing to biologics, cell and gene therapy, RNA therapeutics and vaccines, and beyond, Ginkgo is your cell engineering partner. Our services enable discovery, optimization, and scale up for a wide range of therapeutics modalities.

RNA as a programmable therapeutic

The central challenge of RNA R&D is dialing in the correct RNA sequence. It isn’t the only challenge — any effective RNA therapy also needs to be packaged, delivered and manufactured before it can reach patients. But RNA programming remains key to it all, as it should be informed by and responsive to the comprehensive needs of the greater RNA R&D program.

Ginkgo’s deep expertise in end-to-end biotech R&D and biological programming enables a fully integrated approach to RNA programming. By providing a full package of services, from sequence discovery to delivery assistance, we can streamline the process and help bring effective RNA-based treatments to patients faster and more efficiently.

Watch the event!

A recording of the Virtual Event, Optimizing RNA Therapeutics, is available here.

What will you grow with Ginkgo?