Inhibition of human immunodeficiency virus-1 entry using vectors expressing a multimeric hammerhead ribozyme targeting the CCR5 mRNA
Bibliographic record
Abstract
Rz1-7 is a multimeric hammerhead ribozyme targeting seven unique sites within the human CCR5 mRNA that is active in vitro. Mouse stem cell virus-based MGIN and human immunodeficiency virus (HIV)-1-based HEG1 vectors were used to express Rz1-7 in a human CD4+ T lymphoid cell line. Stable transductants expressed Rz1-7, which was further shown to be active, since CCR5 mRNA and surface CCR5 protein expression levels decreased. High levels of progeny virus were produced when the transduced cells were challenged with an X4-tropic HIV-1 (NL4-3) strain, suggesting that Rz1-7 expression does not affect X4-tropic virus replication. When the transduced cells expressing Rz1-7 were challenged with the R5-tropic HIV-1 (BaL) strain, 99-100% inhibition of progeny virus production was observed for the duration of the experiment (approximately 2 months). When the cells were precultured for 2-3 months prior to HIV-1 infection, inhibition was more prominent in cells transduced with MGIN-Rz1-7 than with HEG1-Rz1-7. Inhibition occurred at the level of viral entry, as no HIV-1 DNA could be detected. These results demonstrate that Rz1-7 confers excellent inhibition of R5-tropic HIV-1 replication at the level of entry. Therefore, we anticipate that this multimeric ribozyme will be beneficial for HIV-1 gene therapy.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".