Products and compositions
The present invention relates to products and compositions and their uses. In particular the invention relates to nucleic acid products that interfere with gene expression or inhibits its expression and therapeutic uses such as for the treatment of disease and disorders.
1. A nucleic acid for inhibiting expression of a target gene in a cell, all nucleotides of the nucleic acid comprising a sugar modified at the 2′ position, and the nucleic acid comprising at least one duplex region that comprises at least a portion of a first strand and at least a portion of a second strand that is at least partially complementary to the first strand, wherein said first strand is at least partially complementary to at least a portion of RNA transcribed from said target gene, wherein (i) the nucleotides of the first strand are modified with alternating 2′ O-methyl modifications and 2′ fluoro modifications, wherein positions 2 and 14 on the first strand starting from the 5′ end are modified with 2′ fluoro, and (ii) the nucleotides of the second strand are modified with 2′ fluoro modifications at positions 11-13 counting from the 3′ end starting at the first position of the double strand region, and the remaining modifications are 2′ O-methyl modifications.
2. The nucleic acid according to claim 1 , wherein the terminal nucleotide at the 3′ end of at least one of the first strand and the second strand is an inverted nucleotide and is attached to the adjacent nucleotide via the 3′ carbon of the terminal nucleotide and the 3′ carbon of the adjacent nucleotide and/or the terminal nucleotide at the 5′ end of at least one of the first strand and the second strand is an inverted nucleotide and is attached to the adjacent nucleotide via the 5′ carbon of the terminal nucleotide and the 5′ carbon of the adjacent nucleotide, or wherein the nucleic acid comprises a phosphorodithioate linkage.
3. The nucleic acid according to claim 1 , conjugated with a ligand.
4. A composition comprising a nucleic acid of claim 1 and a physiologically acceptable excipient.
5. A method of treating a disease or disorder comprising administration of a composition comprising a nucleic acid of claim 1 to an individual in need of treatment.
6. A composition comprising a conjugated nucleic acid of claim 3 and a physiologically acceptable excipient.
7. A method of treating a disease or disorder comprising administration of a composition comprising a conjugated nucleic acid of claim 3 to an individual in need of treatment.