Table 1.

Comparison of in vivo gene transfer and gene editing strategies.

	Gene transfer	Gene editing
Principle	Deliver copy of functional gene	Restore or disrupt endogenous genes
Advantages	•Can treat any patient carrying any variants in a given gene • Does not require DNA breaks • Low risk of integrations with AAV-based vectors • Long-term efficacy • Longer experience in clinical development	• Versatile technology, including base editing and prime editing • Editing of endogenous DNA, potentially conferring permanent efficacy • Can be delivered via viral or LNP systems • Transitory presence of editing machinery and delivery system (LNP) • Re-dosing may be possible when using LNPs
Limitations	• Cannot be “undone” • Current strategies require viral vectors • Adverse events include immune reactions caused by viral capsid • Re-dosing limited by development of neutralizing antibodies • Efficacy may dilute with time if AAV-delivered genetic information persists as episome • Possible development of autoantibodies against newly expressed proteins	• Cannot be “undone” • Only patients with variant in specific target region can be treated • If viral vectors are used, adverse events include immune reactions caused by viral capsid • Possible development of autoantibodies against newly expressed proteins • Risk of off-target editing and unintended effect

AAV, adeno-associated virus; LNP, lipid nanoparticle.