Preclinical Animal Models for Hemophilia Gene Therapy: Predictive Value and Limitations
Bibliographic record
Abstract
Hemophilia A and B are excellent candidate disorders for the application of somatic cell gene therapy. One of the major advantages in the preclinical development of hemophilia gene therapy strategies has been the availability of several animal models for both hemophilia A and B. These models recapitulate many of the phenotypic aspects of human hemophilia and have proven to be very informative in exploring the efficacy and safety of gene therapy. Considerable progress has been made in the design of gene therapy protocols, and over the last 5 years it has been shown that long-term phenotypic correction, with sustained therapeutic levels of factor VIII (FVIII) and factor IX (FIX), can be attained in FVIII- and FIX-deficient mice and dogs using various viral vector-mediated gene therapy approaches. These animal models also have elucidated potential complications of gene therapy protocols, including acute vector-associated toxicities and the induction of neutralizing antibodies to the FVIII and FIX transgene products. Nevertheless, although the preclinical paradigm of hemophilic mouse followed by hemophilic dog studies has proven to be extremely helpful in evaluating the efficacy and safety of potential clinical gene therapy protocols, several limitations to these animal models still exist. This review presents a summary of the animal models available for hemophilia gene therapy, and highlights the various strengths and weaknesses of these models.
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.
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) | 0.001 | 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 | 0.001 | 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".