Prostate‐tumor targeting of gene expression by lentiviral vectors containing elements of the probasin promoter
Bibliographic record
Abstract
BACKGROUND: Lentiviruses are retroviruses that can infect and stably integrate into the chromatin of non-dividing cells. The purpose of this study was to determine whether lentiviral vectors containing the probasin (PB) promoter displayed prostate-specific, androgen-regulated, and persistent gene expression. METHODS: Three lentiviral-PB promoter/enhanced green fluorescent protein (EGFP)-reporter vectors together with a control lentiviral-CMV-EGFP, were tested by microscopy and flowcytometry for expression of EGFP after infection of human prostate cancer cells (LNCaP, PC-3, PC-3(hAR), and Du145 cells) and non-prostate cells (COS-1, HeLa, HeLa(hAR), and MCF-7 cells). RESULTS: All cells infected in vitro with lentiviral-CMV vectors expressed EGFP, whereas with lentiviral-PB vectors (the most potent being Lv-ARR(2)PB), reporter expression was only observed in LNCaP cells with a small amount seen in androgen-independent PC-3 cells. Stable or transient transfection of androgen receptor only raised EGFP expression in prostate-derived cell lines, but did not change tumor specificity. With Lv-ARR(2)PB infected LNCaP cells, androgens regulated EGFP both in vitro and in vivo. After intra-tumor injection of this vector, EGFP expression was observed in LNCaP tumors, but not in A-549 lung or CaKi-2 kidney tumors. CONCLUSIONS: Lv-ARR(2)PB may be an ideal vector for prostate-tumor targeting and for persistent, hormone-enhanced expression of a therapeutic gene to treat slow growing prostate tumors.
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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 | 0.001 | 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".