Table 1.

Comparison of gene addition and genome-editing strategies

	viral-mediated gene addition strategies	HDR-based genome-editing strategies	NHEJ-based genome-editing strategies
Therapeutic gene expression	Depending on the vector copy number and the integration sites	Physiological level expression from endogenous locus Supraphysiological levels from safe harbor, alpha globin locus	–
Efficiency in human HSPCs	Depends on transduction efficiency Transgene, promoter and other regulatory sequences in the vector	Depends on frequency of HDR events, donor types, donor sequences & availability at cut site	Frequency of productive indels
Genotoxic risks	Oncogene transactivation, generation of aberrant transcripts, gene inactivation	Indels at HDR site Off-targets, large genomic rearrangements	Off-targets, large genomic rearrangements
Costs	High (viral delivery)	High (viral delivery)/low (nonviral delivery)	Low (nonviral delivery)