Table 3. Potential and limitations of gene editing strategies at mono- and multigenic level.

Modification	Potential	Limitations	Alternatives
Monogenic	Genetic correction of patient backgrounds provides ideal isogenic controls for in vitro disease modeling (reduced experimental ‘noise')	Strategy cannot be faithfully applied to diseases based on large CNVs (for example, chromosomal deletion syndromes).	(i) Inducible expression of candidate transgene targeted to genomic ‘safe harbor' locus151 (ii) Engineering allelic series into isogenic standard background149
Multigenic	Introduction of additional risk variants or protective alleles into patient backgrounds could provide mechanistic insight into disease modulation and serve as a tool to aggravate or mitigate in vitro phenotypes	Variant modeling studies are complicated by (i) the large number of SNPs in linkage disequilibrium and (ii) limited information to guide the choice of relevant variants.	Automated high-throughput in vitro analysis of patient cohorts stratified according to risk and/or protective factors (Figure 2).

Abbreviation: CNV, copy number varient; SNP, single nucleotide polymorphism.