RNAs for complement inhibition
RNAs, such as miRNA and siRNA, and their use in treating complement-mediated disorders, are described.
1. An miRNA consisting of a nucleotide sequence at least 90% identical to any one of SEQ ID NOs: 76-77 or 79-85, or a portion thereof, wherein the nucleotide sequence is 19-23 nucleotides in length, or an siRNA comprising an antisense strand consisting of the nucleotide sequence.
2. A nucleic acid encoding the miRNA or siRNA of claim 1 .
3. The nucleic acid of claim 2 , comprising any one of SEQ ID NOs: 86-87 or 89-115.
4. An expression vector comprising the nucleic acid of claim 2 .
5. The expression vector of claim 4 , wherein the expression vector is a viral vector.
6. The expression vector of claim 5 , wherein the viral vector is an adeno-associated viral (AAV) vector.
7. The expression vector of claim 4 , further comprising a nucleotide sequence encoding a C3 inhibitor, wherein the C3 inhibitor is an aptamer, an anti-C3 antibody, an anti-C3b antibody, a mammalian complement regulatory protein, or mini factor H.
8. An miRNA consisting of a nucleotide sequence that is at least 90% identical to a nucleic acid sequence that targets nucleotides 617-637, 753-773, 2811-2831, 2835-2855, 3541-3561, 3849-3869, 4125-4145, 4309-4329, and/or 4394-4414 of SEQ ID NO:75, or a portion thereof, wherein the nucleotide sequence is 19-23 nucleotides in length, or an siRNA comprising an antisense strand consisting of the nucleotide sequence.
9. The miRNA or siRNA of claim 1 , wherein the nucleotide sequence is at least 90% identical to SEQ ID NO: 76.
10. A nucleic acid encoding the miRNA or siRNA of claim 9 .
11. The nucleic acid of claim 10 , comprising the nucleotide sequence of SEQ ID NO: 86.
12. An expression vector comprising the nucleic acid of claim 10 .
13. The expression vector of claim 12 , wherein the expression vector is a viral vector.
14. The expression vector of claim 13 , wherein the viral vector is an adeno-associated viral (AAV) vector.
15. The expression vector of claim 12 , further comprising a nucleotide sequence encoding a C3 inhibitor, wherein the C3 inhibitor is an aptamer, an anti-C3 antibody, an anti-C3b antibody, a mammalian complement regulatory protein, or mini factor H.
16. The miRNA or siRNA nucleotide sequence of claim 8 , wherein the nucleotide sequence targets nucleotides 617-637 of SEQ ID NO: 75, or a portion thereof.