Integration Site Analysis Services
In the development of engineered cell therapies, knowing exactly where a viral vector integrates is more than a scientific curiosity, it is a regulatory mandate. Insertional mutagenesis and off-target effects pose significant safety risks that can stall clinical trials or complicate CMC characterization. To move from the bench to the clinic, developers need a validated, high-resolution map of the vector-genome interface.
Integration Site Analysis Services
In the development of engineered cell therapies, knowing exactly where a viral vector integrates is more than a scientific curiosity, it is a regulatory mandate. Insertional mutagenesis and off-target effects pose significant safety risks that can stall clinical trials or complicate CMC characterization. To move from the bench to the clinic, developers need a validated, high-resolution map of the vector-genome interface.
Our Expertise
Avance provides a specialized ligation‑mediated PCR (LM-PCR) based integration site analysis platform designed to meet the rigorous demands of preclinical, clinical, and CMC workflows. Unlike standard methods that may suffer from amplification bias, our LM-PCR approach ensures the precise capture of unknown flanking genomic sequences.
Why LM-PCR?
LM-PCR Workflow Overview
- Complete “Sample-to-Report” Ecosystem: We provide an off-the -shelf assay service that covers every step: DNA extraction, library preparation, sequencing, and expert bioinformatic interpretation.
- Broad-Spectrum Utility: Our LM-PCR workflow provides high-resolution mapping across all different sample types. Beyond reliable integration profiling for Lentivirus and Retrovirus edited cells, we also offer critical detection of unpredictable “random insertions” for AAV or HDR-repair templates, ensuring comprehensive safety characterization even for primarily episomal or targeted editing systems.
- Multi-Platform Versatility: Depending on your resolution needs, we leverage Next-Generation (Short-Read) or 3rd Generation (Long-Read) sequence platforms to ensure the most comprehensive coverage of complex genomic junctions.
- Exceptional Accuracy & Comprehensive Safety Profiling: Our pipeline does not just map sites; it provides cancer-gene cross-referencing. We cross-link integration data with curated oncogene databases to provide an immediate safety profile of your cell population.
- Regulatory Assurance (CFR 21 Part 11): Our data processing is fully Part 11 Compliant, ensuring the audit trails and data integrity required for global regulatory scrutiny.
- Full Lifecycle Support: Whether you are in early-stage research or commercial manufacturing, we offer testing at RUO, GLP, and GMP levels to support Pre-clinical, Clinical, and CMC characterization.
- Rapid Turn-Around Time: We understand that clinical timelines are unforgiving. Our validated workflow is optimized for speed without compromising the depth of analysis.
Additional Integration Site Analysis Services
Methods
Description
Applications
Target Sequencing by Hybridization
Genomic DNA is fragmented and prepared as an NGS library. Target enrichment is performed using hybridization probes specific to vector or transgene sequences, followed by high-throughput sequencing.
Sensitive method for detecting integration junctions without reliance on LTR assumptions. Suitable for diverse integration constructs.
EPTS (Extension Primer Tag Selection) with NGS
A vector- or transgene-specific primer performs linear extension from integration-containing fragments, incorporating a capture tag that enables magnetic enrichment prior to library amplification and sequencing. Enrichment occurs through targeted linear amplification rather than exponential PCR or hybridization capture.
Targeted enrichment of defined transgene integrations with high specificity. Suitable for well-characterized constructs and structured integration analysis.
WGS (Whole Genome Sequencing)
Genomic DNA is sequenced without targeted enrichment using short-read or long-read NGS platforms. Integration sites are identified through computational detection of split reads and structural variants.
Broad genome integrity assessment and clonal cell line characterization. Lower sensitivity for rare integration events compared to targeted enrichment methods.
Technical Information
Explore the power of Next Generation Sequencing (NGS) for biologics development support with our latest whitepaper. Avance Biosciences is at the forefront of NGS testing, offering tailored solutions to support drug development initiatives and GMP manufacturing activities. Delve into real-world case studies, including CRISPR indel amplicon sequencing and insertion site studies, showcasing our expertise in assay development and validation...
