In an interview with PharmaShots, Dr. Bob Deans, Chief Scientific Officer at Synthego shares insights on the wide availability of its new CRISPR-based platform, Eclipse. Synthego created the Eclipse platform to enhance disease modeling, drug target identification, and validation, and accelerate cell therapy manufacturing.

Shots:

• Eclipse uses MLto apply experience from several hundred thousand genome edits across hundreds of cell types. With this machine learning, combined with automation, the new platform can reduce costs and increase the scalability of engineered cell production
• The Eclipse platform is modular in design, allowing for fast deployment of upgrades or add-ons. It is engineered to use a cell-type agnostic process and immediately benefit researchers working with iPS cells and immortalized cell lines
• The platform has enabled large scale Alzheimer's disease research in partnership with the NIH INDI Project

Tuba:  Highlight the key features of the CRISPR-based platform, Eclipse.

Dr. Bob: Eclipse is our newest high-throughput cell engineering platform. Eclipse is designed to accelerate drug discovery and validation by providing highly predictable CRISPR-engineered cells at scale through the integration of engineering, bioinformatics, and proprietary science.

The platform delivers on the new gold standard in cell-based models. It is powered by the learnings of more than 250,000 CRISPR edits and leverages our high-quality synthetic guide RNAs, standardized methods, and machine learning closed-loop feedback. Eclipse performs predictable edits at the scale needed by our customers to meet any experimental size. By using Eclipse, our customers have access to the world’s most reliable CRISPR-based cell models to support disease research.

Tuba:  Discuss the impact of the launch on the company's growth and other activities.

Dr. Bob: We created our Eclipse Platform to make genome editing more precise, scalable, and accessible with the goal of accelerating the research and development of next-generation medicines. The launch of our unique CRISPR-based platform reinforces our position as the genome engineering leader and expands our growing impact on advancing innovation in biopharma R&D.

Tuba:  How will Synthego's platform accelerate drug discovery?

Dr. Bob: We created the Eclipse Platform to enhance disease modeling, drug target identification, and validation, and accelerate cell therapy manufacturing. To ensure the success of any type of edit, Eclipse uses machine learning to apply experience from several hundred thousand genome edits across hundreds of cell types. With this machine learning, combined with automation, Eclipse can reduce costs and increase the scalability of engineered cell production. We engineered Eclipse to use a cell-type agnostic process and immediately benefit researchers working with induced pluripotent stem (iPS) cells and immortalized cell lines.

By industrializing cell engineering, Eclipse will enable economies of scale, turning a historically complex process into one that is flexible, reliable, and affordable. Offering CRISPR edits at scale puts researchers on the cusp of being able to study thousands of genes and examine hundreds of variants of those genes. This will allow scientists to more faithfully model the complexity of a human disease, which could lead to the development of therapeutic drugs or next-generation gene therapies for many serious diseases.

Tuba:  What are the capabilities of the Eclipse Platform?

Dr. Bob: Capabilities include the following:

• Predictive CRISPR design: We eliminate human decision-making bias through data-backed insight. Our comprehensive data collection, machine learning, and bioinformatics fuel a dynamic algorithm to improve every subsequent CRISPR edit.
• Optimized transfection: We conduct comprehensive transfection experiments to maximize editing success. We test variables, including guide design and culture conditions, in high-throughput to achieve the best possible editing outcome.
• Clones with integrity: We optimize automated single-cell isolation to maintain cell health and integrity. For iPS cells, we optimize expansion protocols for pluripotency and genomic stability. Our automated clonal genotyping expedite analysis and ensures accuracy.
• End-to-end tracking: Eclipse's state-of-the-art software manages and tracks massive data sets for editing workflows at any scale, an untenable task for humans.
• Modular design: We designed Eclipse with modularity at the forefront to ensure seamless capacity and capability upgrades as we scale biological diversity with our customers.
• Halo integration: Eclipse leverages our Halo platform to utilize the highest quality CRISPR tools to create the newest gold standard in engineered cells.

Tuba:  What is CRISPR-Cas9? Discuss its applications.

Dr. Bob: CRISPR, or Clustered Regularly Interspaced Short Palindromic Repeats, is a genome engineering technology that enables scientists to easily and precisely edit the DNA of any genome. In nature, the CRISPR palindromic repeats play an important role in microbial immunity. When a virus infects a microbial cell, the microbe employs a special CRISPR-associated nuclease (Cas9) to chop off a piece of the viral DNA. The nuclease is directed to its target sequence by a short RNA fragment known as a guide RNA (gRNA), which is complementary to the target segment of the viral genome. The snipped DNA fragment may then be stored between the palindromic CRISPR sequences to retain a genetic memory for disabling future infections from the same viral strain.

Once scientists learned how the CRISPR system worked in bacteria, they figured out how to reprogram it to allow efficient editing in any species. CRISPR has enabled a simple and affordable way to manipulate and edit DNA, completely changing genome engineering. Although CRISPR is a relatively recent discovery in biotechnology, it has quickly become a standard laboratory tool.

CRISPR-engineered cells have a wide range of applications in research and development across disease areas, including in neuroscience and oncology. CRISPR has already shown promising results for treating several diseases, and researchers are working on new ways to cure diseases, such as cancer, blindness, and Alzheimer’s disease.

Tuba:  Discuss the role of Eclipse in large-scale Alzheimer's disease research in partnership with the NIH iNDI Project.

Dr. Bob: About 50 genes are known to be implicated in Alzheimer's disease and related dementias (ADRD), but their functional dependencies are unknown. Studying these genetic linkages necessitates developing disease models with multiple variants per gene target in a relevant cell type. The U.S. National Institutes of Health (NIH) initiated the Inducible Pluripotent Stem Cell Neurodegeneration Initiative (iNDI) with the goal of creating a library of hundreds of disease models for ADRD studies within the neuroscience community.

The iNDI project required CRISPR-mediated multiple single nucleotide variants (SNVs) per gene across several targets in iPS cells. Scaling CRISPR experiments to generate hundreds of clones is a challenge and serial processes would require years of investment. Furthermore, CRISPR editing a difficult-to-handle cell type like iPS cells is an additional challenge that could impede progress and delay the project further.

Synthego took up this challenging iNDI project, which required the generation of genome-engineered human iPS cell lines harboring ADRD-associated mutations at scale across 22 gene targets. Using our Eclipse platform, we delivered 264 iPS cell clones 12 variants per gene across 22 targets. Our standardized, automated process allowed editing iPS cells in parallel, thus enabling the generation of clones within just a few months.

The iNDI project will generate the largest library yet for neurodegeneration studies, and our generation of industrialized CRISPR iPS cells in a rapid timeframe lays the foundation for a second CRISPR revolution.

Tuba:  Share Synthego's other efforts, beyond the Eclipse platform, to accelerate research and development of next-generation medicines.

Dr. Bob: We also created Halo, an innovative platform that delivers high-quality gene-editing tools to seamlessly support research needs from RUO to GMP reagents. Our Halo Platform powers our CRISPR kits, which include our synthetic sgRNA kit; gene knockout kit v2 for human and mouse-derived cell lines; arrayed human or mouse CRISPR knockout libraries for target discovery; advanced RNA; and synthetic sgRNA GMP manufacturing for CRISPR-based therapeutics and diagnostics. Additionally, we offer engineered cells, including iPS cells, and bioinformatics tools.

Tuba:  Do you provide access to your platforms outside of the U.S.?

Dr. Bob: We support scientists worldwide. To ensure our customers have access to our genome editing portfolio and best-in-class technical support for their CRISPR applications, we partner with authorized distributors around the world, including in the Americas, Europe, and Asia. For more information, visit our worldwide directory.

Image Source: Medical News Today

About Dr. Bob Deans:

Dr. Bob Deans is the Chief Scientific Officer at Synthego.
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