Table 2.

Key differentiating features of RNA- and DNA-based therapies.

RNA AONs	DNA-based therapies
Act at the level of the RNA; do not alter DNA32,35 No DSB generation	Target the DNA; some can directly alter the genome;5,39,40 Induces DSB
Long half-life; require repeat dosing (in IRDs typically once or twice per year)36,41	Potential for single treatment/dosing (per eye); Long-term expression of nuclease
Non-permanent; treatment can be discontinued36,41	Long-term durability still being investigated42–44
Naked, no vectors needed; can target diseases with large, affected genes45	Require viral vectors for delivery; usually limited to diseases with small (trans)gene size36,46 immune response against adeno-associated virus leads to the production of neutralizing antibodies
Can be administered via routine intravitreal injection, using local anesthesia47,48	Usually require subretinal administration; surgery involves vitrectomy and usually requires general anesthesia18,49
Intravitreal administration allows exposure to central and peripheral areas of retina50	Subretinal administration targets usually sub-macular area or the retinal area with available target cells45

RNA: ribonucleic acid; DNA: deoxyribonucleic acid; DSB: double-strand breaks; IRD: inherited retinal disease.