Methods and compounds for the treatment of genetic disease

The transcription modulator molecule as recited in any one of claims 142 and 46, wherein the first terminus has the structure of Formula (A-9):

• or a salt thereof, wherein:
• X1′, Y1′, and Z1′ in each n1 unit are independently selected front CR4, N, NR5, O, or S;
• X2′, Y2′, and Z2′ in each n3 unit are independently selected from CR4, N, NR5, O, or S;
• X3′, Y3′, and Z3′ are independently selected from CR4, N, NR5, O, or S;
• X4′, Y4′, and Z4′ in each n6 unit are independently selected from CR4, N, NR5, O, or S;
• X5′, Y5′, and Z5′ in each n1 unit are independently selected from CR4, N, NR5, O, or S;
• X6′, Y6′, and Z6′ in each n9 unit are independently selected from CR4, N, NR5, O, or S;
• X′, Y7′, and Z7′ in each n11 unit are independently selected from CR4, N, NR5, O, or S;
• X8′, Y8′ and Z8′ are independently selected from CR4, N, NR5, O, or S;
• X9′, Y9′, and Z9′ in each n14 unit are independently selected from CR4, N, NR5, O, or S;
• X10′, Y10′, and Z10′ in each n16 unit are independently selected from CR4, N, NR5, O, or S;
• each R4 is independently H, —OH, halogen, C1-6 alkyl, C1-6 alkoxyl;
• each R5 is independently H, C1-6 alkyl or C1-6alkylamine;
• each n1, n3, n6, n8, n9, n11, n14, and n16 are independently an integer between 0 and 5;
• each n2, n4, n7, n10, n13, and n15 are independently an integer between 0 and 3,
• n1+n2+n3+n4+n5+n6+n7+n8+n9+n10+n11+n12+n13+n14+n15+n16 is between 3 and 18
• or a salt thereof, wherein:
• La is selected from a divalent or trivalent group selected from the group consisting of
• a C1-10 alkylene, —NH—C0-6 alkylene-C(O)—, —N(CH3)—C0-6 alkylene, and
• each R1a and R1b are independently H, or an C1-6 alkyl;
• each m and n are independently an integer between 1 and 10;
• each E1a, E2a, E1b, and E2b, are end groups independently selected front the group consisting of optionally substituted C6-10 aryl, optionally substituted 4-10 membered heterocyclyl, optionally substituted 5-10 membered heteroaryl, an optionally substituted C1-6 alkyl, and optionally substituted amine;
• when La is a trivalent group, the oligomeric backbone is attached to the first terminus through La;
• when La is a divalent group, the oligomeric backbone is attached to the first terminus through one of E1a, E2a, E1b, and E2b, or the oligomeric backbone is attached to the first terminus through a nitrogen or carbon atom on one of five-membered heteroaryl rings.

A compound of structural Formula I:

• X-L-Y (I)
• or a salt thereof, wherein:
• X comprises a recruiting moiety that is capable of noncovalent binding to a regulatory molecule within the nucleus;
• Y comprises a DNA recognition moiety that is capable of noncovalent binding to one or more copies of the pentanucleotide repeat sequence GAA;
• and
• L is a linker.