Speakers
- Dr. Felix Dobbs, Broken String Biosciences (COO), UK
Session Description
Advances in genome editing are enabling cell and gene therapies that offer curative treatment for many diseases. However, unintended off-target DNA breaks remain a key safety concern, as they can drive genomic instability and malignant transformation in edited cells. Comprehensive genome-wide characterisation of on- and off-target breaks is therefore critical across discovery and preclinical development. This need is reinforced by the FDA's April 2026 draft guidance, which recommends NGS-based methods for evaluating off-target editing risk and loss of genome integrity in support of IND applications.
Despite this, sensitive, unbiased methods for therapeutically relevant cells have been limited, relying on indirect readouts, distorted by PCR amplification bias, and an inability to distinguish editing-induced breaks from background damage. These constraints make off-target data difficult to interpret, standardise, and scale.
INDUCE-seq® is a scalable, genome-wide, cell-based platform addressing these limitations through direct, PCR-free mapping of editing-induced DNA breaks, using a novel in situ break-labelling approach coupled with next-generation sequencing. It delivers a sensitive, unbiased, single-nucleotide-resolution readout that characterises on- and off-target sites simultaneously.
This talk presents data linking editing-induced breaks to downstream mutational outcomes, showing why direct detection is essential for safety assessment. We also demonstrate broad applicability across cell types, nuclease systems, and base editing modalities within one standardised workflow.
Session Objectives
- Why direct break detection matters: editing-induced DNA breaks link to downstream mutational outcomes, making direct DSB detection essential for safety assessment.
- Why current methods fall short: indirect readouts, no therapeutic cell context, PCR bias, and an inability to separate editing-induced breaks from background damage.
- How INDUCE-seq® solves this: PCR-free, in situ break-labelling with NGS for a sensitive, unbiased, single-nucleotide-resolution readout of on- and off-target sites directly in any therapeutically relevant cell.
- One workflow, full landscape: works across cell types, nuclease systems, and base editing modalities.
- Regulatory alignment: INDUCE-seq supports the FDA's April 2026 draft guidance on NGS-based off-target assessment for IND applications.
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