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Record W2009066388 · doi:10.2174/156652308785160674

CCR5 as Target for HIV-1 Gene Therapy

2008· review· en· W2009066388 on OpenAlex

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.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueCurrent Gene Therapy · 2008
Typereview
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsUniversity of Toronto
Fundersnot available
KeywordsChemokine receptorChemokine receptor CCR5BiologyCXCR4ChemokineC-C chemokine receptor type 6Immune systemVirologyCCR1ReceptorImmunologyGenetics

Abstract

fetched live from OpenAlex

Acquired immune deficiency syndrome (AIDS) is caused by a lentivirus, human immunodeficiency virus type-1 (HIV-1). Viral entry is mediated by specific interaction of the viral envelope (Env) glycoprotein with a cell surface molecule CD4 which serves as the primary receptor and a chemokine (C-C or C-X-C motif) receptor CCR5 or CXCR4 which serves as a co-receptor. The viral Env, the cellular CD4 receptor, or the CCR5/CXCR4 co-receptors may be the targets of therapeutic interventions. Compared to the high variability of the viral Env protein, lack of variability in the CD4 receptor and the CCR5 or CXCR4 co-receptor makes them better targets to prevent viral entry. Downregulation of CD4 or CXCR4 is likely to have harmful consequences for the immune function or cellular maturation and homing. In contrast, individuals who lack functional CCR5 have no apparent immune defects, and show decreased susceptibility to HIV-1 infection and delayed progression to AIDS. CCR5 is essential for HIV-1 infection through all routes of transmission. Therefore, its downregulation may not only prevent disease progression, but also the spread of HIV-1 transmission. To block CCR5 function, a number of molecules were developed, including low molecular weight compounds, chemokines, N-terminally-modified chemokine analogues, chemokine-derived molecules, chemokine-based synthetic peptides, and anti-CCR5 monoclonal antibodies. Gene therapy strategies were developed using intrakines and intrabodies to prevent cell surface expression of CCR5 and zinc finger-nucleases, or using small interfering RNAs, antisense RNAs, or ribozymes to decrease co-receptor synthesis. This review describes the importance of targeting CCR5 and summarizes the status of various anti-CCR5 gene therapy strategies.

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 imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesInsufficient payload (model declined to judge)
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.946
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.009

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.

Opus teacher head0.112
GPT teacher head0.389
Teacher spread0.278 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it