DNA breaks drive cancer, ageing, and neurodegeneration. They are also the biggest safety obstacle in gene therapy, and the warning sign of drug toxicity. POLEX™ resolves them at base resolution across the whole genome, including the centromeres and satellite regions short-read methods cannot read.
Every drug-development decision, biomarker, and treatment choice that involves DNA damage rests on a measurement. The method shapes what you see. Three methods dominate the field. Each has a hard limit that decides which applications it can serve.
An indirect marker. Counts spots of phosphorylated H2AX as a proxy for nearby breaks. Today's standard pharmacodynamic readout in clinical trials.
Damage measured by the length of a DNA "comet tail" in a gel under microscopy. Decades old. Still widely used in genotoxicity work.
Capture-based methods using 50 to 300 bp Illumina reads. Direct break detection at base resolution, but only where reads can be uniquely mapped.
Therapeutic radiation hits centromeres and pericentric heterochromatin hardest. γH2AX foci saturate at clinical doses. Short-read methods can't map the centromeric breakage that drives mitotic catastrophe. POLEX™ resolves it.
Cytosolic DNA fragments trigger innate-immunity priming. Most of them come from centromeric DNA stuck in micronuclei. Conventional methods can't trace origin. POLEX™ identifies the genomic source.
rDNA breakage is increasingly linked to neurodegeneration. But rDNA is invisible to short-read sequencing. POLEX™ reads through ribosomal repeats. New damage axis, now measurable.
POLEX™ measures the on-target DNA damage signature of a compound at every step, from target validation through preclinical optimisation. Base resolution. Repetitive regions included.
Quantify compound-induced DNA damage with dose response. Catch tox liabilities early. Cuts late-stage attrition. Works in primary cells, iPSCs, and organoids.
Break rate per Mb · lesion class · strand bias · dose response
For PARP, ATR, ATM, WEE1, USP1, PARP7, and DNA-PK programmes. Show where in the genome target inhibition drives damage. Turns MoA claims into mappable evidence.
Target engagement · MoA fingerprint · pathway preference
Map on- and off-target breaks from CRISPR, base editors, and prime editors at single-read resolution. Catches off-targets in repeats where GUIDE-seq and amplicon sequencing fail.
Off-target atlas · repair outcome · editor fidelity score
Once a compound enters the clinic, POLEX™ supports the readouts that drive trial decisions. Patient stratification. Dose escalation. Response prediction. Resistance tracking.
Quantify break burden, repair-deficiency signatures, and HRD status from FFPE or fresh tumour tissue at single-base resolution. Complements existing genomic and IHC workups.
SSB/DSB burden · HRD signature · repair fingerprint
Quantitative DSB induction in patient-matched material. A PD readout for Phase Ia/Ib dose escalation. Separates on-target damage from off-target toxicity in a way viability assays cannot.
Pre vs on-treatment delta · dose response · per-patient PD curve
Test several DDR drugs on a patient-derived organoid. Rank by induced break burden. Recommend therapy. Catches acquired resistance (like BRCA reversion) that genomic testing alone misses.
Per-patient drug ranking · resistance flags · therapy recommendation
Areas where direct DNA-break measurement has been underused because conventional methods couldn't deliver the resolution. POLEX™ changes the calculus.
For external-beam, brachytherapy, and the next-generation radioligand pipeline (PSMA-617, DOTATATE class). Map radiation-induced DSB landscapes at therapeutic doses. Characterise off-target damage. Support dosimetry.
Per-region DSB density · LET signature · dose response
For DDR plus checkpoint blockade combination programmes. Quantify the breaks that drive cytosolic DNA, micronucleus formation, and cGAS-STING activation. The molecular trigger for innate-immunity priming.
Cytosolic-DNA origin · STING surrogate · combo synergy
For Alzheimer's, ALS, Parkinson's, and longevity research. Detect break accumulation in postmitotic neurons. Resolve damage in repetitive neuronal regions where conventional methods are blind. New therapeutic axis.
Longitudinal break accumulation · region-specific damage · pathway gaps
Where each indication sits in our internal pipeline.
We run pilot studies, custom analyses, and full-service collaborations. Reach out and we’ll scope it with you.
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