Exon skipping by peptide nucleic acid derivatives

A peptide nucleic acid derivative represented by Formula I, or a pharmaceutically acceptable salt thereof:

• wherein,
• n is an integer between 10 and 25;
• the compound of Formula I possesses at least a 10-mer complementary overlap with a 14-mer target splice site sequence that consists of 7-mer from intron and 7-mer from exon within a target pre-mRNA;
• the compound of Formula I is fully complementary to the target pre-mRNA sequence, or partially complementary to the target pre-mRNA sequence with one or two mismatches;
• S1, S2, . . . , Sn-1, Sn, T1, T2, . . . , Tn-1, and Tn independently represent deuterido [D], hydrido [H], substituted or non-substituted alkyl, or substituted or non-substituted aryl radical;
• X and Y independently represent hydrido, formyl [H—C(═O)—], aminocarbonyl [NH2—C(═O)—], aminothiocarbonyl [NH2—C(═S)—], substituted or non-substituted alkyl, substituted or non-substituted aryl, substituted or non-substituted alkylacyl, substituted or non-substituted arylacyl, substituted or non-substituted alkyloxycarbonyl, substituted or non-substituted aryloxycarbonyl, substituted or non-substituted alkylaminocarbonyl, substituted or non-substituted arylaminocarbonyl, substituted or non-substituted alkylaminothiocarbonyl, substituted or non-substituted arylaminothiocarbonyl, substituted or non-substituted alkyloxythiocarbonyl, substituted or non-substituted aryloxythiocarbonyl, substituted or non-substituted alkylsulfonyl, substituted or non-substituted arylsulfonyl, substituted or non-substituted alkylphosphonyl, or substituted or non-substituted arylphosphonyl radical;
• Z represents hydrido, hydroxy, substituted or non-substituted alkyloxy, substituted or non-substituted aryloxy, non-substituted amino [—NH2], substituted or non-substituted alkylamino, substituted or non-substituted arylamino, substituted or non-substituted alkyl, or substituted or non-substituted aryl radical;
• B1, B2, . . . , Bn-1, and Bn are independently selected from natural nucleobases including adenine, thymine, guanine, cytosine and uracil, and unnatural nucleobases;
• and
• at least four of B1, B2, . . . , Bn-1, and Bn are independently selected from unnatural nucleobases with a substituted or non-substituted amino radical covalently linked to the nucleobase moiety.