Webinar: Genome Stability Assessment

Building Confidence in Engineered iPSC Lines: A Case Study in Genome Stability Assessment

This presentation, led by Erin Cross (VP of Platform, KROMATID) and Daniel O’Connell (Consultant), explores advances in genomic integrity testing and strategies for de-risking genome editing in cell and gene therapy development.

Key Topics Covered

• Emerging Editing Platforms

  • Overview of Tome Biosciences and CRISPR-directed integrases

  • Reverse transcriptase, Cas9 nickase, and integrase-based insertion strategies

• KROMASURE InSite Analysis

  • Evaluation of on-target vs. off-target insertions

  • Structural rearrangements and optimization of experimental conditions

  • Use of ddPCR quantification for precision analysis

• Genomic Integrity Roadmap for iPSC Cell Therapies

  • Multi-layer testing approaches: WGS, Karyostat, and KROMASURE

  • Detecting rare structural variants at single-cell resolution

  • Ensuring IND-readiness through workflow validation

• Cell Line and Donor Evaluation

  • Data-driven donor and engineered cell line selection

  • Comparative karyotyping and variant calling for quality control

• Integrated Genomic Characterization

  • Complementary use of cytogenetics and sequencing

  • Orthogonal strategies to detect both small variants and large structural changes

  • Framework for variant de-risking based on cancer relevance and prevalence

• KROMATID’s Role in Next-Gen Cytogenetics

  • Cytogenetic testing for event prevalence, structural characterization, and genomic stability

  • Rare-event detection with higher sensitivity compared to traditional cytogenetics

  • Enabling confident decisions around safety, efficacy, and regulatory compliance

• Regulatory and Safety Context

  • FDA guidance on human gene therapy products with genome editing

  • Importance of evaluating off-target effects, mutagenesis, and karyotype integrity

Overall Message
Understanding and monitoring genomic integrity early in development enables safer, more efficient allogeneic therapies, accelerates the path to clinic, and strengthens regulatory submissions.