siRNA compounds and methods of use thereof
OwnerElena Feinstein, Hagar Kalinski +2inventors
InventorsElena Feinstein, Hagar Kalinski, Igor Mett, Evgenia Alpert
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Abstract
The present invention relates to compounds, pharmaceutical compositions comprising same and methods of use thereof for the inhibition of certain genes, including SOX9, ASPP1, CTSD, CAPNS1, FAS and FAS ligand. The compounds and compositions are useful in the treatment of subjects suffering from diseases or conditions and or symptoms associated with diseases or conditions in which gene expression has adverse consequences.
Claims27
A compound having the structure:
- 5′(N)x—Z3′ (antisense strand)
- 3′Z′—(N′)y-z″5′ (sense strand)
- wherein each of N and N′ is a ribonucleotide which may be unmodified or modified, or an unconventional moiety;
- wherein each of (N)x and (N′)y is an oligonucleotide in which each consecutive N or N′ is joined to the next N or N′ by a covalent bond;
- wherein Z and Z′ may be present or absent, but if present is independently 1-5 consecutive nucleotides covalently attached at the 3′ terminus of the strand in which it is present;
- wherein z″ may be present or absent, but if present is a capping moiety covalently attached at the 5′ terminus of (N′)y;
- each of x and y is independently an integer between 18 and 40;
- wherein the sequence of (N′)y is substantially complementary to the sequence of (N)x;
- and
- wherein (N)x comprises an antisense sequence present in any of Tables A-AQ.
A method of treating a subject suffering from a disease or condition selected from a neurodegenerative disease or disorder including spinal cord injury, Alzheimer's disease (AD) and Amyotrophic Lateral Sclerosis (ALS);
- acute renal failure (ARF);
- hearing loss;
- an ophthalmic disease including glaucoma and ischemic optic neuropathy (ION);
- a respiratory disease including acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD) and other acute lung and respiratory injuries;
- injury (e.g. ischemia-reperfusion injury) in organ transplant including lung, kidney, bone marrow, heart, pancreas, cornea or liver transplantation;
- nephrotoxicity, pressure sores, dry eye syndrome or oral mucositis, comprising administering to the subject an siRNA compound which inhibits expression of a gene selected from SOX9, ASPP1, CTSD, CAPNS1, FAS and FAS ligand in an amount effective to treat the disease or condition.
A method of treating a subject suffering from a disease or condition selected from the group consisting of spinal cord injury, Alzheimer's disease (AD) and Amyotrophic Lateral Sclerosis (ALS) comprising administering to the subject an siRNA which inhibits expression of a gene selected from SOX9, ASPP1, CTSD, CAPNS1, in an amount effective to treat the disease or condition.
A method of treating a subject suffering from an ophthalmic disease or condition selected from the group consisting of glaucoma, ION and an eye disease secondary to diabetes comprising administering to the subject an siRNA which inhibits expression of a gene selected from SOX9, ASPP1, CTSD, CAPNS1, in an amount effective to treat the disease or condition.
A method of treating a subject suffering from dry eye syndrome comprising administering to the subject an siRNA which inhibits expression of a gene selected from FAS and FAS ligand in an amount effective to treat the disease or condition.
Dependencies are inferred from the claim text.