Figure and Table | Antisense Oligonucleotide-Mediated Exon-skipping Therapies: Precision Medicine Spreading from Duchenne Muscular Dystrophy

Table 1. Antisense Oligonucleotides (ASOs) to Treat Duchenne Muscular Dystrophy (DMD).

Name	ASO			Target exon	Phase
Name	Nucleic acid	Size	Route	Target exon	Phase
Eteplirsen	PMO	25	IV	51	Approved
Golodirsen	PMO	25	IV	53	Approved
Viltolarsen	PMO	21	IV	53	Approved
Casimersen	PMO	25	IV	45	Approval stage
Renadirsen	ENA/2'RNA	18	SC	45	I/II

Table 2. Gene Functional Changes Induced by Exon Skipping.

Function	Target exon	Gene	Inheritance	Disease
Restoration	Normal out-of-frame	DMD	Monogenetic	DMD
	Mutated in-frame exon	DYSF	Monogenetic	LGMD2B
	Mutated out-of-frame exon	SGCG	Monogenetic	LGMD2C
	Mutated pseudo exon	CLRN1	Monogenetic	USH3
Destruction	Out-of-frame exon	MSTN	Non monogenetic	Diabetes mellitus
Modulation	Normal in-frame exon	ITGA4	Non monogenetic	Crohn’s disease

Table 3. Skipping of Normal Out-of-frame Exons.

Disease	Gene	Exon	Phase	Author, Year
DMD	DMD	51, 53, 45	A, W, I/II	Schneider et al. 2021 ⁽²⁵⁾
Dysferlinopathy	DYSF	51	P	Verwey et al. 2020 ⁽²³⁾
Parkinson’s disease	PRKN	4	P	Li et al. 2020 ⁽²⁴⁾

Table 4. Skipping of Mutated In-frame Exons.

Disease	Gene	Exon	Phase	Author, Year
LGMD2B	DYSF	32	P	Barthelemy et al. 2015 ⁽²⁶⁾
Laminopathy	LMNA	5	P	Scharner et al. 2015 ⁽²⁷⁾
Joubert syndrome	CEP290	41	P	Molinari et al. 2019 ⁽³¹⁾
Alport syndrome	COL4A5	21	P	Yamamura et al. 2020 ⁽²⁹⁾
Dystrophic epidermolysis bullosa	COL7A1	73	P	Bornert et al. 2020 ⁽³⁰⁾
CADASIL	NOTCH3	9	P	Gravesteijn et al. 2020 ⁽³²⁾
Mucolipidosis II	GNPTAB	19	P	Matos et al. 2020 ⁽³³⁾
Myotonic dystrophy type1	DMPK	15	P	Stepniak et al. 2020 ⁽³⁴⁾

Table 5. Skipping of Mutated Out-of-frame Exons.

Disease	Gene	Exon	Phase	Author, Year
LGMD2C	SGCG	4-7	P	Wyatt et al. 2018 ⁽³⁵⁾
CADASIL	NOTCH3	2-3,4-5,6	P	Rutten 2016 ⁽³⁸⁾
HGPS	LMNA	11	P	Lee et al. 2016 ⁽³⁶⁾
SCA3	ATXN3	10	P	McIntosh et al. 2019 ⁽³⁷⁾

Table 6. Skipping of Pseudoexons.

Disease	Gene	Phase	Author, Year
Usher syndrome type III	CLRN1	P	Panagiotopoulos et al. 2020 ⁽⁴¹⁾
LGMD2B	DYSF	P	Dominov et al. 2020 ⁽⁴²⁾
Erythropoietic protoporphyria	FECH	P	Halloy et al. 2020 ⁽⁴³⁾
Stargardt disease	ABCA4	P	Sangermano et al. 2019 ⁽⁴⁴⁾
Neuronal ceroid lipofuscinosis 7	CLN7	H	Kim et al. 2019 ⁽⁴⁵⁾

Table 7. Skipping of Out-of-frame Exons for the Disruption of Gene Function.

Disease	Gene	Exon	Phase	Author, Year
Diabetes mellitus	MSTN	2	P	Eilers et al. 2021 ⁽⁵⁰⁾
DMD	MSTN	2	P	Kemaladewi et al. 2011 ⁽⁴⁷⁾
Parkinson’s disease	LRRK2	41	P	Korecka et al. 2020 ⁽⁴⁸⁾
Prostate cancer	ERG	4	P	Li et al. 2020 ⁽⁴⁹⁾
Muscle fibrosis	ALK5	6	P	Kemaladewi et al. 2014 ⁽⁵¹⁾
Familial hypercholesterolemia	APOB	27	P	Disterer et al. 2013 ⁽⁵²⁾

Table 8. Skipping of Normal In-frame Exons.

Disease	Gene	Exon	Lost domain	Phase	Author, Year
Crohn’s disease	ITGA4	27	transmembrane	P	Aung-Htut 2019 ⁽²¹⁾
Dupuytren’s disease	ALK5	2	ligand binding	P	Karkampouna et al. 2014 ⁽⁵³⁾
Muscle fibrosis				P	Kemaladewi et al. 2014 ⁽⁵¹⁾
Hypertrophic scar				P	Raktoe et al. 2020 ⁽⁵⁴⁾
Cancer	CD44	v8	ligand binding	P	Fukushima et al. 2020 ⁽⁵⁵⁾