Compositions and methods for inhibiting Factor D
The application discloses methods and compositions for the inhibition of the alternative complement pathway. The methods and compositions involve the use of aptamers for inhibiting complement Factor D. The application further provides anti-Factor D aptamers for the treatment of dry age-related macular degeneration, geographic atrophy, wet age-related macular degeneration or Stargardt disease.
1. An aptamer that selectively blocks a catalytic cleft of complement Factor D (fD), wherein said aptamer comprises a nucleic acid sequence that does not comprise any one of SEQ ID NOs: 73-80.
2. The aptamer of claim 1 , wherein said aptamer inhibits a function associated with fD.
3. The aptamer of claim 1 , wherein said aptamer is an RNA aptamer or a modified RNA aptamer.
4. The aptamer of claim 1 , wherein said aptamer is a DNA aptamer or a modified DNA aptamer.
5. The aptamer of claim 1 , wherein said aptamer inhibits a function of fD with an IC 50 of about 50 nM or less as measured by an alternative complement-dependent hemolysis assay.
6. The aptamer of claim 1 , wherein said aptamer inhibits activity of fD as compared to a control when measured by a fD esterase activity assay.
7. The aptamer of claim 1 , wherein said aptamer inhibits activity of fD as measured by a hemolysis assay.
8. The aptamer of claim 1 , wherein said aptamer selectively binds to fD with a K d of less than about 50 nM.