Table 1.

Three broad approaches to e-GE with potential human applications

Approach	Examples	Method
Correcting disease by targeting the disease genes	Fragile X syndrome Huntington disease spinocerebellar ataxia myotonic dystrophy Huntington disease, spinocerebellar ataxia, and myotonic dystrophy	altering the methylation pattern of gene promotors to restore gene function
	β-thalassaemia sickle cell disease	epigenome modification enables disease correction through derepressing aberrantly silenced genes and upregulating expression of related genes that compensate for the null mutations
	Angelman Prader-Willi Pitt-Hopkins Rett	e-GE could be used to activate the silenced allele
Augment efficacy of existing therapies	tumor suppressors and oncogenes (e.g., EGFR in breast and gastric cancers)	e-GE can reduce oncogenic overexpression, thereby halting or slowing tumor growth
	overcoming drug resistance (e.g., PARP inhibitors, such as rupacarib in ovarian cancer)	the use of e-GE would allow existing drugs to be used in drug-resistant patients and minimize potentially harmful side effects through allowing lower effective doses
Enhancing phenotypic traits	deactivating or activating non-disease genes may enable cell lineage switching or controlled expression of proteins in cells that result in desired phenotypic outcomes (e.g., erythropoietin for enhanced athletic performance)	such modalities could enable performance enhancing modifications without the direct use of hormones or drugs