Reliable assessment of genome-editing safety begins with accurate detection and quantification of structural variants. For cell and gene therapy programs, confidence in next-generation sequencing (NGS) data is essential to understanding potential genotoxic effects. Increasingly, regulatory bodies are emphasizing potential long-term genotoxic effects of cell and gene therapies. For gene editing approaches, this includes large scale structural variants (e.g. chromosomal translocations, off-target integrations). However, sequencing the entire genome to high depth is neither computationally nor financially feasible. GeneGoCell’s Genome Editing Verification (GEV℠) service portfolio G-Trans℠ platform is a proprietary sample-to-report solution that utilizes ligation-mediated PCR, semi-specific target-amplification sequencing to exam genome-wide translocation events caused by or related to the editing of target-of-interest. The platform includes assay design, sample preparation, sequencing, and custom data analysis. G-Trans℠ is built for accuracy, customizability, efficiency, and quality, delivering scalability and tailored support. All sample testing are completed with a guaranteed two-week turnaround time.
G-Trans℠: Genome-wide Translocation Analysis
Double-stranded breaks (DSBs) generated during editing events have the potential to create large-scale chromosomal rearrangements (e.g. translocations). Stable, balanced translocations can be highly genotoxic and cancerous, which has become a critical part of safety profiling required by various regulatory agencies globally. Using adapter-ligated UMIs (see below) and a semi-specific PCR approach (Figure 1), G-Trans℠ is designed to specifically capture genome-wide translocation events between target editing site and anywhere in the genome. This approach has been validated under GMP guidelines to accurately report translocations with Limit of Detection (LOD) as sensitive as 0.005%.
Unique Molecular IDs
In order to analyze native molecules and minimize PCR amplification-introduced bias, G-Trans℠ incorporates unique molecular IDs (UMIs) such that each original genomic copy of DNA found in a sample are barcoded once with a UMI, allowing for accurate quantification and tracking during data analysis. As opposed to PCR-introduced UMIs, this ligation-mediated approach is the gold standard for molecular barcoding. UMIs minimizes PCR bias, reduce false positive variant calls, and enable accurate quantification.
Expert Project Support from Start to Finish
At GeneGoCell, we understand the unique needs from our clients when it comes to their proprietary technologies and platforms. That’s why we customize every project to meet your unique goals: from experimental design to data analysis and reporting. Our dedicated team of experienced project managers, scientists, and PhD-level bioinformaticians collaborate to provide seamless, end-to-end support for each individual project.
About GeneGoCell, Inc.
As a GxP/CLIA-compliant, ISO/IEC 17025:2017-accredited laboratory based in San Diego, we are deeply committed to the highest standards of data integrity and regulatory readiness. With a proven track record of quality and scientific rigor, we’ve supported over 100+ clients across the globe. Our testing and results have been used in 30+ successful IND filing packages. Our team is currently providing GxP-compliant lot-release testing for 10+ clinical trial programs. Our experienced project managers work closely with you providing end-to-end support, ensuring every step is aligned with your program’s specific goals and compliance needs. Wherever you are in your development journey, we’re here to provide reliable, high-quality NGS support.
GEV doesn’t have to be complicated. We’ve simplified the process from start to finish, with quick onboarding, minimal hands-on time for your team, and results delivered in as little as 3 days. Our experts handle the details so you can stay focused on your research and development goals. Contact our team for a complimentary consultation with our SME for G-Trans Panel feasibility review, discuss your G-Trans Panel, get a customized testing plan or request a quote. We are happy to share the technical White Paper about our G-Trans℠ upon request.
Learn more about G-Trans℠ and find out how GeneGoCell’s Genome-Editing Verification (GEV)℠ platform can be tailored to meet your specific goals and help advance life-changing therapies.
Disclaimer: All Rights Reserved. All content (text, images, code) described by GeneGoCell is copyright of GeneGoCell, Inc unless specifically stated. GeneGoCell is a GxP/CLIA-compliant, ISO/IEC 17025:2017 accredited, (CFR Title 21 Part 58) testing company.