Cell-penetrating peptide conjugates and methods of their use

A pharmaceutical composition comprising

• a conjugate, or a pharmaceutically acceptable salt thereof, is of the following structure having a glutamic acid residue:
• wherein the peptide consists of the sequence RBRRBRFQILYBRBR (SEQ ID NO:
• 35) and is covalently linked to the glutamic acid residue at the C-terminus of the peptide, wherein the peptide is acetylated at its N-terminus;
• and
• wherein the oligonucleotide is a PMO and consists of the sequence 5′-CTCCAACATCAAGGAAGATGGCATTTCTAG-3′ (SEQ ID NO:
• 195), wherein the oligonucleotide is linked by its 3′-terminus to the glutamic acid residue and has the following group at its 5′ terminus:
• and
• a pharmaceutically acceptable carrier.

A pharmaceutically acceptable salt of

• a conjugate of the following structure having a glutamic acid residue:
• wherein the peptide consists of the sequence RBRRBRFQILYBRBR (SEQ ID NO:
• 35) and is covalently linked to the glutamic acid residue at the C-terminus of the peptide, wherein the peptide is acetylated at its N-terminus;
• and
• wherein the oligonucleotide is a PMO and consists of the sequence 5′-CTCCAACATCAAGGAAGATGGCATTTCTAG-3′ (SEQ ID NO:
• 195), wherein the oligonucleotide is linked by its 3′-terminus to the glutamic acid residue and has the following group at its 5′ terminus:

A pharmaceutical composition comprising

• a pharmaceutically acceptable salt of a conjugate of the following structure having a glutamic acid residue:
• wherein the peptide consists of the sequence RBRRBRFQILYBRBR (SEQ ID NO:
• 35) and is covalently linked to the glutamic acid residue at the C-terminus of the peptide, wherein the peptide is acetylated at its N-terminus;
• and
• wherein the oligonucleotide is a PMO and consists of the sequence 5′-CTCCAACATCAAGGAAGATGGCATTTCTAG-3′ (SEQ ID NO:
• 195), wherein the oligonucleotide is linked by its 3′-terminus to the glutamic acid residue and has the following group at its 5′ terminus:
• and
• a pharmaceutically acceptable carrier.