Table 2.

Nucleic-acid-based molecules in preclinical studies and clinical trials for DM1.

Molecule Class	Target	Therapeutic Molecule	Mechanism	DDS	Admin. Route	Study Phase	Ref
ASOs	DMPK CUGexp	PMO-CAG25, 2′-OMe-CAG, LNA-CAG mixmers, all-LNA-CAG	MBNL1 binding block	Naked	IM	Preclinical	[92,103,104,105]
	DMPK CUGexp	PPMO-B, PPMO-K; Pip6a-PMO	MBNL1 binding block	CPP-conj	IM, IV	Preclinical	[106,107]
	DMPK CUGexp	miniPEG-γ PNA	MBNL1 binding block	Polymer-conj	SC	Preclinical	[108,109]
	DMPK 3′UTR	MOE gapmers, c-Et gapmers, LNA gapmers	DMPK mRNA degradation	Naked	IM, SC, ICV	Preclinical	[54,70,110,111,112]
	DMPK CUGexp	LNA gapmers, MOE gapmers	Mutated DMPK mRNA degradation	Naked	IM	Preclinical	[113]
	DMPK 3′UTR	IONIS-DMPKRx	DMPK mRNA degradation	Naked	SC	Clinical(completed)	[114]
	DMPK 3′UTR	palmitoyl-c-Et gapmers	DMPK mRNA degradation	Lipid-conj	SC	Preclinical	[69]
	miRNAs targeting Mbnl1 mRNA	cholesterol-2′OMe-ASOs	AntagomiR	Lipid-conj	SC, IV	Preclinical	[115,116]
	Mbnl1 3′UTR	Pip9b2-PMO	BlockmiR	CPP-conj	IV	Preclinical	[117]
siRNA	DMPK CUGexp	siRNA-CAG	Mutated DMPK mRNA degradation	Nacked	IM	Preclinical	[118]
	DMPK mRNA	AOC 1001	DMPK mRNA degradation	Ab-conj	IV	Clinical (recruiting)	[119]
rAAV	DMPK downstream pathway	MBNL1	MBNL1 overexpression	rAAV1	IM	Preclinical	[120]
	DMPK downstream pathway	MBNL1	Competition for CUGexp interaction	rAAV9	IM	Preclinical	[121]
	DMPK CTG spanning region	Sa/eSpCas9-sgRNAs	CTGexp removal	rAAV9	IM	Preclinical	[122,123]
	DMPK CTGexp	dSaCas9-sgRNA	Transcription inhibition	rAAV6, rAAV9	IV	Preclinical	[124]
	DMPK CUGexp	RCas9-sgRNA	DMPK mRNA degradation	rAAV9	IV, TA	Preclinical	[125]

Abbreviations: Ab-conj = antibody-conjugated; Admin. Route = administration route; CPP = cell-penetrating peptide; CTGexp = CTG expansion; CUGexp = CUG expansion; DDS = drug delivery system; dSaCas9 = deactivated Staphylococcus aureus Cas9; ICV = intracerebroventricular; IM = intramuscular; IV = intravenous; Naked = not conjugated ASOs; rAAV = recombinant adeno-associated virus; RCas9 = RNA targeting Cas9; RO = retro orbital; eSpCas9-sgRNAs = enhanced Streptococcus pyogenes Cas9-single guide.