Protease-Deleted Adenovirus Vectors and Complementing Cell Lines: Potential Applications of Single-Round Replication Mutants for Vaccination and Gene Therapy
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
A new kind of versatile adenoviral vector (AdV) has been constructed, one that is completely replication disabled in the absence of Ad-E1 proteins but is capable of a single round of replication when Ad-E1 is present. This was made possible by deletion of the Ad protease gene (PS), which is essential for many steps of the Ad life cycle. The PS-deleted virus can be propagated in 293-derived cell lines engineered to express PS. In these new complementing cells, the PS gene was expressed from a tetracycline-inducible promoter in a dicistronic vector coexpressing the green fluorescent protein (GFP). When induced, the best 293-PS stable clones produced the PS in amounts greater than the level reached after Ad infection. Biological activity was first demonstrated by the ability of 293-PS cells to support the replication of Ad2ts1, a mutant expressing a functionally defective PS. While overexpression of the Ad PS slightly affected cell growth, moderate expression at levels sufficient to fully complement Ad2ts1 was well tolerated in 293 cells. Two PS-deleted mutants, deleted or not deleted for E1/E3, were then generated and characterized. Despite their complete loss of infectivity after a single round of replication in permissive cells, the PS-deleted mutants produced as much viral protein as wildtype Ad. These new vectors should thus be both safer and more efficient for applications in which enhancement of transgene expression is desirable, as in the case of vaccination, in situ therapy for tumors, protein production, or the large-scale production of other viral vectors such as adeno-associated virus (AAV).
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.
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 it