Discovery and Characterization of Small-molecule CRISPR/Cas13 Inhibitors Using a High Throughput Platform
Bibliographic record
Abstract
Since being re-purposed for gene editing in mammalian cells, the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas (CRISPR Associated Protein) system has become an indispensable resource in the molecular biologist’s toolbox. This family of RNAguided endonucleases cleaves RNA or DNA sequences in a sequence-specific manner. CRISPR/Cas13 has received attention due to its ability to specifically target ssRNA sequences. The goal of this thesis was to expand the capabilities of this system by enabling small-molecule control of its activity. To do this, we screened a library of 13,120 compounds for the ability to inhibit CRISPR/LwCas13a activity in vitro using a fluorescent assay. Next, we validated the top 20 hits using both fluorescent and native substrate assays. We characterized verified compounds and evaluated their activity in cells. These results identify new cell permeable Cas13 inhibitors that enable its activity to be regulated in cells with unprecedented ease.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 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 | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".