Direct delivery of Cas9 or base editor protein and guide RNA complex enables genome editing in the retina
Bibliographic record
Abstract
Abstract Genome editing by CRISPR-Cas holds promise for the treatment of retinal dystrophies. For therapeutic gene editing, transient delivery of CRISPR- Cas9 is preferable to viral delivery which leads to long-term expression with potential adverse consequences. Successful delivery of Cas9 protein and its guide RNA as ribonucleoprotein (RNP) complexes has been reported in the retinal pigment epithelium in vivo but not into photoreceptors, the main target of retinal dystrophies. Here, we investigate the feasibility of direct RNP delivery to photoreceptors and RPE cells. We show that RNPs composed of Cas9 or adenine- base editor and guide RNA, without addition of any carrier compounds, induce gene editing in retinal cells at variable rates depending on the guide RNA efficiency and on the locus. But Cas9 RNP delivery at high concentrations leads to outer retinal toxicity indicating a need to improve delivery efficiency for future therapeutic use.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".