Early Changes in Liver Transcriptomic Profiles Following Adeno-Associated Viral Gene Therapy in the Severe Hemophilia A Dog Model
Bibliographic record
Abstract
Introduction Recombinant adeno-associated virus vectors (rAAV) are a major gene therapy platform for treatment of monogenic disorders, including hemophilia A. Valoctocogene roxaparvavec (AAV5-HLP-hFVIII-SQ) is an AAV5 vector delivering B-domain-deleted (BDD) human FVIII transgene controlled by a hybrid liver-selective promoter. In a phase 3 trial, a single treatment of AAV5-HLP-hFVIII-SQ (6e13 vg/kg) provided therapeutic expression of FVIII and bleeding control in adult severe hemophilia A patients. However, the mechanistic basis of transaminitis, variability and durability observed in clinical trial participants are not clear. Understanding the molecular changes in the liver are critical to identify appropriate immune modulatory strategies for safety, efficacy, and long-term durability of AAV gene therapy. The aim is to investigate liver gene expression profiles before and after AAV5-HLP-canine-BDD-FVIII (cFVIII) administration in a severe hemophilia A dog model.
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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 | 0.001 |
| 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".