108. Pseudotyping Baculovirus Based Vectors for Enhanced In Vitro and In Vivo Delivery
Bibliographic record
Abstract
Autographa californica multinucleopolyhedrovirus (AcMNPV) is the best-characterized baculovirus and the platform for well established recombinant protein and vaccine production technologies. In addition to countless examples of recombinant protein production, two commercially available vaccines (Cervarix, and Provenge) are produced via AcMNPV based expression technologies. More recently, Baculovirus based vectors have also garnered attention as gene delivery vectors, including for use in human gene therapy, because of several key characteristics. Baculoviruses can transduce cells of human origin, albeit at MOIs of 100-200, can accommodate large gene insertions (>38 kb), allowing for the inclusion of multiple genes, large promoters, and regulatory elements, are non-replicative in mammalian cells, do not integrate into mammalian chromosomes, and humans lack pre-existing immunity to baculoviruses. In vivo, Baculoviruses have been used to successfully transduce a wide variety of organs from mammalian species, such as mice, rats and rabbit. Despite these reports there is little information on the overall tissue distribution of in vivo delivered baculovirus. Here we test the transduction efficiency of wildtype and pseudotyped baculovirus vectors in various cell lines, and define the biodistribution of these vectors in C57BL/6 mice via intravenous, intrahepatic, and intranasal installation. In vitro, wildtype virus demonstrated good transduction of HEK293 cells and moderate to low transduction of cells originating from the lung and liver. Amongst the pseudotypes tested, the greatest transduction achieved across all cell types (in vitro) was a recombinant displaying a cell-penetrating-peptide-GP64 fusion protein (CPP-GP64), which demonstrated high levels of transduction across all cell lines tested. In vivo, overall transduction by wildtype virus was restricted to the kidneys and liver, and only at moderate to low levels. Similar to the in vitro results, inclusion of a CPP-GP64 greatly enhanced the transduction levels as well as expanded the tissue distribution of in vivo delivered vector.
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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 | 0.000 | 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) | 0.000 | 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".