. Author manuscript; available in PMC: 2022 Jan 1.

Published in final edited form as: Adv Drug Deliv Rev. 2020 May 7;168:118–133. doi: 10.1016/j.addr.2020.05.001

Table 3.

Comparisons of gene therapy strategies for GHL.

	Gene replacement	Gene silencing		Gene editing
	Gene replacement	RNAi	ASOs	CRISPR-Cas9	Base editor
Mechanism	Overriding the faulty gene with the correct copy	Post-transcriptional RNA degradation	Inducing RNase H cleavage of targets	NHEJ/HDR	Deaminating activity
Phenotype and genotype	Recessive homologous	Dominant heterozygous	Dominant heterozygous/recessive homologous	Dominant heterozygous/recessive homologous
Molecular target	None	RNA	RNA	DNA	DNA
Target modulation	Knockin	Knockdown	Knockdown	Knockout or knockin	Base substitution
Off-target rate	None	High	High	Low or moderate	Low or moderate
Sustained time	Short	Short	Short	Permanent	Permanent
Delivery form	cDNA	dsRNA	ssDNA/ssRNA	cDNA/mRNA/protein	cDNA/mRNA/protein
Delivery strategy	Viral vectors	Viral vectors, lipid and polymer nanoparticles.		Viral vectors, electroporation, microinjection, lipid and polymer nanoparticles.
Examples	Gjb2, Tmc1, Whrn, Otof, Clrn1, Ush1c, Lhfpl5, MsrB3, Kcnq1, VGLUT3	Gjb2, Tmc1	Slc26a4, Ush1C	Slc26a4, Tmc1, Cdh23	Ctnnb1
Reference	[33, 34, 46, 47, 53–56, 101–108]	[32, 48, 49]	[9, 37, 100]	[16–19]	[20]