Rates of homology directed repair of CRISPR-Cas9 induced double strand breaks are lower in naïve compared to primed human pluripotent stem cells
Bibliographic record
Abstract
Gene editing in human pluripotent stem cells (hPSC) is a powerful tool for understanding biology, for drug discovery and gene therapy. Naïve hPSC have been suggested to be superior for gene editing compared to conventional ‘primed’ hPSC. Using droplet digital PCR, we uncover the kinetics of Cas9-induced double strand break repair in conventional hPSC. Cut but unrepaired alleles reach their maximum after 12–24 h. Homology directed repair plateaus after 24 h, whereas repair by non-homologous end joining continues until 48 h after Cas9 introduction. Using this method, we demonstrate that the rate of homology directed repair to resolve Cas9-induced double strand breaks is 40% lower in naïve hPSC compared to conventional hPSC, correlating with, and feasibly explained by, a higher number of cells in G1 phase of the cell cycle in naïve hPSC. Therefore, naïve hPSC are less efficient for CRISPR/Cas9-mediated homology directed repair.
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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".