Education | 2024-01-16

Application:

Cytogenomics

Cell & Gene Therapy Development

Product:

Saphyr System

Rachel Steinberg

In the ever-evolving landscape of biological research, the preservation and quality control of cell biorepositories plays a pivotal role in advancing scientific discoveries and breakthroughs. Travis Hardcastle, a senior product manager specializing in Engineered Cells at Synthego, is making waves in the field by exploring the utility of optical genome mapping (OGM) for quality control in cell biorepositories.   

In this blog post, we’ll delve into the significance of his team’s work and the potential it holds for the scientific community.   

The Essence of Cell Biorepositories   

Cell biorepositories serve as treasure troves of biological samples, housing various cell types critical for research across multiple disciplines, from genomics to drug development. In particular, cell biorepositories of human pluripotent stem cells (hPSCs) are essential for preclinical and clinical research and applications. Over time, long-term cultured hPSCs can develop and accumulate recurrent genomic abnormalities and copy number variations that can be detrimental to basic research. Some copy number variations, such as the common 20q11.21 amplification, can lead to selective advantages and reduce differentiation capacities. Therefore, it is critical to monitor the genomic integrity of hPSC cultures as a key quality control measure. Ensuring the integrity and authenticity of these hPSCs is paramount, as any discrepancies or abnormalities can lead to erroneous results and wasted research development & manufacturing efforts.   

The Role of Optical Genome Mapping   

At its core, cytogenetics is a branch of genetics that studies the DNA structure within the cell’s nucleus. Karyotyping is a tool or technique that cytogeneticists use to study the structure of DNA in the nucleus. These approaches can vary from staining and imaging, sequencing, microarray, or polymerase chain reaction (PCR) based applications.  The shortfall of current tools to detect structural variants (SVs) can have huge consequences. If a detrimental SV, such as the common 20q11.21 abnormality, isn’t discovered in a cell line, a researcher’s data can be potentially compromised. Even worse, it can lead to compromising a patient’s safety in clinical applications. Additionally, without these discoveries, fewer new cell and gene therapies end up being approved in manufacturing (the current success rate for Phase 2 through approval is only 14%). Optical genome mapping is a solution that addresses these critical gaps, detecting SVs with high resolution, much faster TAT when compared with traditional methods, and complete genome-wide coverage without the need to use multiple techniques. This method for cell & gene therapy R&D can potentially significantly improve the quality, safety, and overall risk profile of next-generation therapy development & manufacturing.  

Travis Hardcastle’s Innovative Approach   

Hardcastle and his team at Synthego have recognized the potential of OGM to serve as a powerful tool for quality control during the discovery and early research phase. They focus on using CRISPR/Cas9 technology to generate disease models and recapitulate disease phenotypes in common cancer cell lines and hPSCs, specifically for early-stage researchers. The vision of Synthego is to provide researchers with a high throughput platform that enables them to study disease phenotypes at scale. To that end, OGM enables Synthego to maintain a biorepository of five high-quality, in-house hPSCs for quickly initiating genome editing projects. They are integrating the OGM workflow technology into the quality assessment process to ensure the genetic integrity of cryopreserved in-house cell lines. By comparing the genomic profiles of cryopreserved cells with reference genomes, researchers can quickly identify any anomalies or deviations, such as chromosomal aberrations or genetic mutations.   

Advantages of Mr. Hardcastle’s & Synthegos’ Research   

1. Enhanced Data Reliability: Incorporating optical genome mapping into cell biorepository quality control protocols can significantly reduce the risk of using genomically compromised cell lines for creating genetically modified disease models. This, in turn, enhances the reliability and reproducibility of research outcomes.   

2. Time and Cost Efficiency: Traditional methods of quality control can be time-consuming and expensive. Optical genome mapping offers a rapid and cost-effective alternative that expedites the assessment process without compromising accuracy.   

3. Broad Applicability: Mr. Hardcastle’s work isn’t limited to a specific research field. It has the potential to benefit a wide range of scientific disciplines, from cancer research to stem cell studies and beyond.   

The Future of Cell Line Integrity with OGM 

With continued advancement in karyotyping technology, like what have seen over the past decade, and specifically with the introduction of OGM technology, we suspect that further chromosomal abnormality will be discovered in many more hPSCs currently being used in research labs across the globe.  

As Mr. Hardcastle and Synthego continue to explore the utility of optical genome mapping in quality control for cell biorepositories, we can expect to see significant advancements in the way biological samples are preserved and maintained. His work represents a crucial step forward in the field of cell biorepository quality control. Utilizing the OGM end-to-end workflow can ensure researchers of the integrity of their cell lines and help unlock new possibilities in cell and gene therapy development research. As this technology becomes more widely adopted, we can anticipate a brighter spotlight for cytogenomics.