Early postnatal expression mitigates immune responses to Cas9 in the murine central nervous system
Bibliographic record
Abstract
Cas9 in neonatal vs. adult mice. Injection of AAV-Cas9s containing either a neuron-specific synapsin promoter, or a cytomegalovirus promoter, into neonatal mice resulted in robust expression of Cas9 and activation of microglia. Expression of Cas9 was maintained 3 months post-injection while the microglial response dissipated by this time. In contrast, infusion of AAV-Cas9s into the adult brain resulted in the absence of detectable Cas9 protein and reduced neuronal density. Activation of microglia and astrocytes, T cell infiltration into the CNS, and circulating antibodies were also observed. Surprisingly, these effects were not seen in adult mice administered an AAV encoding EGFP. The lack of detectable Cas9 protein in the adult injected mice indicates that Cas9-expressing neurons were eliminated via a cytotoxic immune response. Our findings suggest that very early postnatal administration may enhance safety and efficacy in treatments for pediatric disorders employing CRISPR-Cas9 gene editing.
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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 | 0.005 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".