Enhanced HDR-mediated correction of heterozygous COL7A1 mutations for recessive dystrophic epidermolysis bullosa
Bibliographic record
Abstract
mutations not previously targeted by existing gene therapies. Editing was achieved using Cas9-nuclease ribonucleoproteins with short single-stranded DNA donor templates, and outcomes were assessed with an Oxford Nanopore Technology sequencing analysis pipeline. We demonstrate precise genomic HDR rates of up to 75% of alleles in primary RDEB keratinocytes and 32% in fibroblasts. This approach restored collagen VII expression in up to 80% of keratinocytes within a bulk-edited population and resulted in correct collagen VII deposition in a 3D skin model. Additionally, at one locus we show that a dual Cas9-nickase strategy is less effective than Cas9-nuclease and prone to large on-target deletions. Our results demonstrate a significant advancement in the efficiency and consistency of HDR editing, potentially paving the way for more effective personalized gene therapies.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".