Current develoments and future prospects for HIV gene therapy using interfering RNA-based strategies
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
Acquired immunodeficiency syndrome (AIDS) is a slow, progressive, degenerative disease of the human immune system, ultimately leading to premature death of the patient. This disease is primarily caused by human immunodeficiency virus type-1 (HIV-1). The major targets of HIV infection are blood cells, namely lymphocytes and macrophages. While the immune response fails to eliminate the infected cells, the virus continues to spread. The purpose of HIV gene therapy is to provide "anti-HIV" genes to cells that are susceptible to HIV infection. Anti-HIV genes may be designed to express RNAs or proteins that interfere with the function of viral or cellular RNA(s)/protein(s), thereby inhibiting virus replication. Whereas interfering proteins may be cytotoxic and/or immunogenic, interfering RNAs are not. Interfering protein-based strategies requiring inducible gene expression (under the control of HIV regulatory proteins) can only be designed to block steps subsequent to the viral regulatory protein production. In contrast, interfering RNAs can be produced in a constitutive manner, which further enhances their antiviral activity and allows one to design strategies to inhibit virus replication before viral regulatory protein production occurs. Thus, interfering RNAs are of particular interest and are the focus of this review. Genes expressing interfering RNAs were designed to inhibit syncytium formation to prevent the death of the gene-modified cells. Strategies may also be developed to prevent gene-modified cells from becoming infected by HIV or from supporting HIV replication. Genes expressing interfering RNAs have been designed to inhibit HIV-1 entry and to cleave the incoming virion RNA, thus blocking virus replication before provirus DNA synthesis can be completed. A number of genes were also designed to express interfering RNAs that inhibit HIV replication at a post-integration step, by inhibiting the function of HIV RNAs or proteins produced in the infected cell. Also in development are anti-HIV genes that produce RNAs that would not only inhibit HIV replication in the gene-modified cell, but also prevent HIV RNA packaging and/or reverse transcription such that the progeny virus produced would be non-infectious. Further refinements to these strategies may lead to the development of "self-propagating" anti-HIV genes. These genes would express interfering RNAs that not only inhibit virus replication in the cell and prevent HIV RNA packaging and/or reverse transcription in the progeny virus, but also make use of the HIV itself to deliver the anti-HIV gene(s) to other cells. Thus, more and more cells susceptible to HIV infection would become resistant. Such "self-propagation" of anti-HIV-1 genes would only occur in cells that are susceptible to HIV infection, and would continue to take place for as long as HIV exists in the body.
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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) | 0.001 | 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