Compositions and methods for regulating complement system
OwnerSamuel Reich, Nadine Dejnekainventors
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Abstract
The disclosure provided herein provides for methods and compositions for modulating the human complement pathway by reducing the expression or production of one or more complement pathway protein and uses for such methods for treating diseases including ocular disease and macular degeneration related disease. The invention also includes active agents for mediating the modulation of the complement pathway including siRNA designed to cause the RNAi-mediated degradation of complement pathway proteins.
Claims53
An isolated siRNA comprising:
- a sense RNA strand having a nucleotide sequence substantially identical to a target sequence of from about 19 to about 25 contiguous nucleotides of human C3 protein mRNA;
- and
- an antisense RNA strand having a sequence substantially complementary to the sense RNA strand;
- wherein the sense RNA strand and the antisense RNA strand form an RNA duplex.
A pharmaceutical composition comprising:
- an effective amount of an isolated siRNA having a sense RNA strand including a nucleotide sequence substantially identical to a target sequence of about 19 to about 25 contiguous nucleotides in human C3 protein mRNA and an antisense RNA strand substantially complementary to the sense RNA strand, wherein the sense and an antisense RNA strands form an RNA duplex, and
- a pharmaceutically acceptable carrier.
A method for inhibiting expression of human complement system or complement system regulator mRNA comprising:
- administering to a subject in need thereof an effective amount an isolated siRNA having a sense RNA strand including a nucleotide sequence substantially identical to a target sequence of about 19 to about 25 contiguous nucleotides in human C3 protein mRNA and an antisense RNA strand substantially complementary to the sense RNA strand, wherein the sense and an antisense RNA strands form an RNA duplex;
- and
- degrading the human C3 regulatory mRNA wherein degrading the human C3 regulatory mRNA inhibits expression of the human C3 regulatory mRNA and inhibits initiation and/or proliferation of a complement system response.
A method of treating a disease in a subject, comprising:
- administering to the subject an effective amount of an isolated siRNA having a sense RNA strand including a nucleotide sequence substantially identical to a target sequence of about 19 to about 25 contiguous nucleotides in human C3 protein mRNA and an antisense RNA strand substantially complementary to the sense RNA strand, wherein the sense and an antisense RNA strands form an RNA duplex;
- and
- degrading C3 RNA in the subject.
A method of treating an ocular disorder associated with drusen comprising:
- ocularly administering to at least one eye of a subject an effective amount of an isolated siRNA having a sense RNA strand including a nucleotide sequence substantially identical to a target sequence of about 19 to about 25 contiguous nucleotides in human C3 protein mRNA and an antisense RNA strand substantially complementary to the sense RNA strand, wherein the sense and an antisense RNA strands form an RNA duplex;
- and
- degrading C3 mRNA in the at least one eye of the subject.
Dependencies are inferred from the claim text.