In the original article, there was a mistake in Table 1 as published. The references indicated in row B are wrong. The corrected Table 1 appears in the attached below.
Table 1.
Integration strategies | Advantages | Disadvantages | References | ||
---|---|---|---|---|---|
A | Endogenous locus | Physiological transgene expression Corrects multiple mutations |
Gene-specific strategy Limited to gene body mutations |
Urnov et al., 2005; Lombardo et al., 2007; Li et al., 2011; Genovese et al., 2014; Voit et al., 2014; Dever et al., 2016; Hubbard et al., 2016; Schiroli et al., 2017; Sweeney et al., 2017; Kuo et al., 2018; Wang et al., 2019; Rai et al., 2020; Wang L. et al., 2020 | |
B | Superactive promoters (ALB, HBA) | Accommodates different transgenes Supraphysiological expression Few integrations required |
Partial gene disruption Limited to non-cell autonomous disorders Extensive validation required |
Barzel et al., 2015; Sharma et al., 2015; Davidoff and Nathwani, 2016; Laoharawee et al., 2018; Chen et al., 2019; Conway et al., 2019; De Caneva et al., 2019; Ou et al., 2019, 2020; Zhang et al., 2019; Wang Q. et al., 2020 | |
C | Tolerant to integration (AAVS1, CCR5, Rosa26) | Accommodates different transgenes | Artificial promoters required Variable expression |
De Ravin et al., 2016; Diez et al., 2017; Stephens et al., 2018, 2019; Gomez-Ospina et al., 2019; Scharenberg et al., 2020 | |
D | Chromatin domains (NAD) | Fine gene regulation Far from oncogenic genes |
No proof-of-principle in clinically relevant models | Schenkwein et al., 2020 | |
E | Disease-modifier genes (CCR5, HBA) | Improve therapeutic effect Lower therapeutic threshold |
Extensive validation required Limited to well-known diseases |
Voit et al., 2013; Wiebking et al., 2018 | |
F | Specificity Exchange (TCR, BCR) |
Improved CAR expression and potency | Off-targets Translocations risk (for multiple edits) |
Eyquem et al., 2017; MacLeod et al., 2017; Greiner et al., 2019; Hartweger et al., 2019; Moffett et al., 2019; Voss et al., 2019 |
Scissors: nuclease; Solid arrows: promoters; Enh, enhancers; TAD, topologically associating; d, domain; Solid ovals: histone modifications; Solid squares: DNA modifications.
The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.
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