RNA interference in skin indications
The present invention relates to RNAi constructs with improved tissue and cellular uptake characteristics and methods of use of these compounds in dermal applications.
1. A method for treating compromised skin, the method comprising, administering to a subject a therapeutically effective amount for treating compromised skin of a double stranded nucleic acid molecule comprising a guide strand, with a minimal length of 16 nucleotides, and a passenger strand forming a double stranded nucleic acid molecule, having a double stranded region and a single stranded region, the double stranded region having 8-15 nucleotides in length, the single stranded region having 4-12 nucleotides in length, wherein position 1 of the guide strand is 5′ phosphorylated or has a 2′ O-methyl modification, wherein the passenger strand is linked to a lipophilic group, wherein at least 40% of the nucleotides of the double stranded nucleic acid are modified, and wherein the double stranded nucleic acid molecule has one end that is blunt or includes a one nucleotide overhang, wherein the double stranded nucleic acid molecule is directed against a gene encoding Connective Tissue Growth Factor (CTGF), and wherein treating compromised skin comprises preventing, reducing, or inhibiting dermal scarring in compromised skin.
2. The method of claim 1 , wherein the subject has a wound.
3. The method of claim 2 , wherein the wound is a result of elective surgery.
4. The method of claim 1 , wherein the double stranded nucleic acid molecule is administered on the skin of the subject in need thereof.
5. The method of claim 1 , wherein the nucleic acid molecule is administered by local injection.
6. The method of claim 1 , wherein the single stranded region contains 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 phosphorothioate modifications.
7. A method for treating compromised skin, the method comprising, administering to a subject a therapeutically effective amount for treating compromised skin of a double stranded nucleic acid molecule comprising a guide strand, with a minimal length of 16 nucleotides, and a passenger strand forming a double stranded nucleic acid molecule, having a double stranded region and a single stranded region, the double stranded region having 8-15 nucleotides in length, the single stranded region having 4-12 nucleotides in length, wherein position 1 of the guide strand is 5′ phosphorylated or has a 2′ O-methyl modification, wherein at least 40% of the nucleotides of the double stranded nucleic acid are modified, and wherein the double stranded nucleic acid molecule has one end that is blunt or includes a one nucleotide overhang, wherein the double stranded nucleic acid molecule is directed against a gene encoding Connective Tissue Growth Factor (CTGF), and wherein treating compromised skin comprises preventing, reducing, or inhibiting dermal scarring in compromised skin.
8. The method of claim 7 , wherein the subject has a wound.
9. The method of claim 8 , wherein the wound is a result of elective surgery.
10. The method of claim 7 , wherein the double stranded nucleic acid molecule is administered on the skin of the subject in need thereof.
11. The method of claim 7 , wherein the nucleic acid molecule is administered by local injection.
12. The method of claim 7 , wherein the single stranded region contains 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 phosphorothioate modifications.