Deletion of VAI and VAII RNA Genes in the Design of Oncolytic Adenoviruses
Bibliographic record
Abstract
Deletion of viral functions that can be complemented by the specific phenotype of tumor cells is a common strategy to design oncolytic viruses. For example, enhanced mRNA cytoplasmic export in tumor cells phenocopies the adenovirus E1B-55K function and renders mutants of this protein tumor selective. Also, an activated RB pathway complements specific E1A functions that can be deleted to produce oncolytic viruses. In this paper we demonstrate that an adenoviral mutant deleted in virus-associated I (VAI) and VAII RNAs (Ad-VAdel) has oncotropism characterized by 100-fold replication deficiency compared with wild-type adenovirus in normal cells and an unaffected ability to replicate and kill different types of tumor cells. This mutant also displays active antitumoral activity in vivo. In contrast, this oncotropism is less evident in a mutant expressing an inactive form of VAI (Adsub719) because VAII RNA expression is upregulated. The mRNA translation promoted by VA RNA genes can be phenocopied in tumor cells with the activation of signal transduction pathways, such as the Ras pathway.
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 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 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".