Exon skipping by peptide nucleic acid derivatives

A peptide nucleic acid derivative represented by Formula I, or a pharmaceutically acceptable salt thereof, for inducing exon skipping by targeting intron/exon or exon/intron junction of pre-mRNA:

• wherein,
• n is an integer between 11 and 20;
• 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 are hydrido radical;
• X is hydrido radical;
• Y is substituted or non-substituted alkyloxycarbonyl radical;
• Z is amino 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 five of B1, B2, . . . , Bn-1, and Bn are independently selected from unnatural nucleobases represented by Formula II, Formula III, or Formula IV:
• wherein,
• R1, R2, R3, R4, R5 and R6 are hydrido radical;
• L1, L2 and L3 are a covalent linker represented by Formula V covalently linking the basic amino group to the nucleobase moiety:
• wherein,
• Q1 and Qm are substituted or non-substituted methylene (—CH2—) radical, and Qm is directly linked to the basic amino group;
• Q2, Q3, . . . , and Qm-1 are independently selected from substituted or non-substituted methylene or oxygen radical;
• and
• m is an integer between 1 and 15.