329. Identifying Pharmacological Enhancers of Adenoviral Vector Replication and Transgene Expression
Bibliographic record
Abstract
Adenovirus (Ad) vectors are currently the most commonly used vehicle for therapeutic gene delivery in human gene therapy, and oncolytic Ad-based gene therapy has shown promise in several types of cancer. We are interested in identifying compounds that enhance or inhibit Ad gene expression and replication.We have designed a novel Ad vector containing the RFP gene within the late transcription unit. Thus, the level of RFP expression correlates to the extent of virus replication. We have also validated a high-throughput system for screening small molecules using this vector. The anticancer chemotherapy drug vorinostat was initially expected to increase gene expression from the vector since it is a pan-histone deacetylase inhibitor (HDACI), and HDACIs have been shown to increase Ad transgene expression. However, our assays show that vorinostat significantly delays the onset of vector replication and transgene expression, and that these effects may be specific to the inhibition of class I HDACs. We are currently working on elucidating the mechanism by determining the role of specific class I HDACs and the downstream effects of HDAC-activity loss. Consequences of HDAC inhibition on vector replication and transgene expression will also be studied in vivo. In the future, we will use our Ad construct to screen small-molecule libraries and identify novel enhancers of these processes.
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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".