| Autor: |
Ethan Deitcher, Kirk Trisler, Branden S. Moriarity, Caleb J. Bostwick, Fleur A. D. Leenen, Steven R. Deitcher |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
BioMedInformatics, Vol 4, Iss 2, Pp 1384-1395 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2673-7426 |
| DOI: |
10.3390/biomedinformatics4020076 |
| Popis: |
Genome engineered B-cells are being developed for chronic, systemic in vivo protein replacement therapies and for localized, tumor cell-actuated anticancer therapeutics. For continuous systemic engineered protein production, expression may be driven by constitutively active promoters. For actuated payload delivery, B-cell conditional expression could be based on transgene alternate splicing or heterologous promotors activated after engineered B-cell receptor (BCR) stimulation. This study used a bioinformatics-based approach to identify putative BCR-stimulated gene promoters. Gene expression data at four timepoints (60, 90, 210, and 390 min) following in vitro BCR stimulation using an anti-IgM antibody in B-cells from six healthy donors were analyzed using R (4.2.2). Differentially upregulated genes were stringently defined as those with adjusted p-value < 0.01 and a log2FoldChange > 1.5. The most upregulated and statistically significant genes were further analyzed to find those with the lowest unstimulated B-cell expression. Of the 46 significantly upregulated genes at 390 min post-BCR stimulation, 6 had average unstimulated expression below the median unstimulated expression at 390 min for all 54,675 gene probes. This bioinformatics-based identification of 6 relatively quiescent genes at baseline that are upregulated by BCR-stimulation (“on-switch”) provides a set of promising promotors for inclusion in future transgene designs and engineered B-cell therapeutics development. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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