Table 3.
Comparison of EB therapy approaches
| Gene therapy | Cell therapy | RNA‐targeting therapy | Protein therapy (g) | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Gene replacement (a) | Gene editing (b) | Revertant cell therapy (mosaicism) (c) | BM‐SC Tx (d) | Other cell types (fibroblasts, MSCs) (e) | AON | PTC | SMaRT | ||
| Advantages | |||||||||
| Systemic application feasible | − | −/+ | − | + | −/+ | + | + | − | + |
| Long‐term correction | + | + | + | − | − | − | − | − | − |
| Specific (gene/sequence) targeting | − | + | − | − | − | + | − | + | − |
| Personalized therapy | − | +/− | + | − | − | + | + | + | + |
| Applicable for | |||||||||
| Recessive EB forms | + | + | + | + | + | + | + | + | + |
| Dominant EB forms | − | + | +/− | N/A | N/A | + | − | + | (+) |
| Combination therapy reasonable with | (e) | (e), iPSCa | iPSC | − | (a), (b), iPSC | − | − | − | − |
| Limitations | |||||||||
| Tumorigenesis | + + (insertional mutagenesis) | − | − | + (immunosuppression) | +/− (immunosuppression) | unk | unk | unk | − |
| Estimated risk of off‐target effects | ++ | + | − | − | − | + | + | + | − |
| Risk of adverse immunological response | + | + | − | + | + | + | + | + | + |
| Major side effects | − | unk | − | + (procedure related) | − | unk | unk | unk | unk |
| Invasiveness | + | + | + | + | − | − | − | − | − |
| High degree of complexity | ++ | ++ | + | + | − | − | − | − | − |
| Efficiency | ++ | + | N/A | N/A | N/A | + | N/A | N/A | N/A |
Abbreviations: ++, to a very great extend; +, largely true; +/−, partly true; −, not true, unk, unknown; N/A, not applicable, (+), theoretically possible.
a
iPSC, induced pluripotent stem cells, differentiated into other cell types (eg keratinocytes, fibroblasts).