|
Type |
Applicable scenarios |
Verification required |
|
Broad spectrum promoter |
Maximize model coverage or rapid verification |
Different tissue strengths, silencing, immunity and toxicity |
|
Tissue/cell type promoter |
Restrict transcription to target cells |
Species conservation, size and activity in disease states |
|
Enhancer + minimal promoter |
More fine cell subtype selection |
Orientation/copy number, cross-species migration and leakage |
|
miRNA de-targeting |
Depress non-target expression in liver, immune cells, etc. |
Endogenous miRNA abundance, saturation and tissue differences |
|
Induction system |
Time control or reversible adjustment |
Leaky expression, inducer exposure and expression cassette capacity |
Cross-species enhancer research from 2016 to 2020 proved that short regulatory elements can achieve finer neuronal subtype selection than traditional large promoters; however, enhancer performance is still affected by species, brain regions, load and minimal promoter combinations. Specificity, positive rate, expression intensity per unit cell and expression cassette size should be compared at the same time when selecting. [11-1 to 11-3]
References for this chapter
[11-1] Dimidschstein J, et al. A viral strategy for targeting and manipulating interneurons across vertebrate species. Nat Neurosci. 2016;19:1743-1749. DOI:10.1038/nn.4430. PMID:27798629. [H]
[11-2] Jüttner J, et al. Targeting neuronal and glial cell types with synthetic promoter AAVs in mice, non-human primates and humans. Nat Neurosci. 2019;22:1345-1356. DOI:10.1038/s41593-019-0431-2. PMID:31285614. [H]
[11-3] Vormstein-Schneider D, et al. Viral manipulation of functionally distinct interneurons in mice, non-human primates and humans. Nat Neurosci. 2020;23:1629-1636. DOI:10.1038/s41593-020-0692-9. PMID:32807948. [H]
[11-4] Wang JH, et al. AAV as a delivery vector for gene therapy of human diseases. Signal Transduct Target Ther. 2024;9:78. DOI:10.1038/s41392-024-01780-w. [N/H]