A double stranded nucleic acid molecule having structure set forth below: 5' N 1 - x - Z 3' (antisense strand) 3' Z'-N 2 -(N')y -z" 5' (sense strand) wherein each of N 2, N and N' is an unmodified or modified ribonucleotide, or an unconventional moiety; wherein each of x and (N')y is an oligonucleotide in which each consecutive N or N' is joined to the adjacent N or N' by a covalent bond; wherein each of x=y=18; wherein the sequence of x has complementarity to a consecutive sequence in a target RNA; and the sequence of N 2 -(N')y is fully complementary to the sequence of N 1 - x; wherein N 1 is covalently bound to x and mismatched to the target RNA; wherein: when the pairing nucleotide in the target RNA is adenosine, uridine in position 1 of the antisense strand is substituted with an N 1 selected from adenosine or deoxyadenosine; or when the pairing nucleotide in the target RNA is cytidine, guanosine in position 1 of the antisense strand is substituted with an N 1 selected from adenosine, deoxyadenosine, or deoxyuridine; or when the pairing nucleotide in the target RNA is guanosine, cytidine in position 1 of the antisense strand is substituted with an N 1 selected from adenosine or deoxyadenosine; or when the pairing nucleotide in the target RNA is uridine, adenosine in position 1 of the antisense strand is substituted with an N 1 which is deoxyuridine; wherein z" may be present or absent, but if present is a capping moiety covalently attached at the 5' terminus of N 2 -(N')y; and wherein each of Z and Z' is independently present or absent, but if present is independently 1-5 consecutive nucleotides, consecutive non-nucleotide moieties or a combination thereof covalently attached at the 3' terminus of the strand in which it is present. wherein each of N 2, N and N' is an unmodified or modified ribonucleotide, or an unconventional moiety; wherein each of x and (N')y is an oligonucleotide in which each consecutive N or N' is joined to the adjacent N or N' by a covalent bond; wherein each of x=y=18; wherein the sequence of x has complementarity to a consecutive sequence in a target RNA; and the sequence of N 2 -(N')y is fully complementary to the sequence of N 1 - x; wherein N 1 is covalently bound to x and mismatched to the target RNA; wherein: when the pairing nucleotide in the target RNA is adenosine, uridine in position 1 of the antisense strand is substituted with an N 1 selected from adenosine or deoxyadenosine; or when the pairing nucleotide in the target RNA is cytidine, guanosine in position 1 of the antisense strand is substituted with an N 1 selected from adenosine, deoxyadenosine, or deoxyuridine; or when the pairing nucleotide in the target RNA is guanosine, cytidine in position 1 of the antisense strand is substituted with an N 1 selected from adenosine or deoxyadenosine; or when the pairing nucleotide in the target RNA is uridine, adenosine in position 1 of the antisense strand is substituted with an N 1 which is deoxyuridine; wherein z" may be present or absent, but if present is a capping moiety covalently attached at the 5' terminus of N 2 -(N')y; and wherein each of Z and Z' is independently present or absent, but if present is independently 1-5 consecutive nucleotides, consecutive non-nucleotide moieties or a combination thereof covalently attached at the 3' terminus of the strand in which it is present. when the pairing nucleotide in the target RNA is adenosine, uridine in position 1 of the antisense strand is substituted with an N 1 selected from adenosine or deoxyadenosine; or when the pairing nucleotide in the target RNA is cytidine, guanosine in position 1 of the antisense strand is substituted with an N 1 selected from adenosine, deoxyadenosine, or deoxyuridine; or when the pairing nucleotide in the target RNA is guanosine, cytidine in position 1 of the antisense strand is substituted with an N 1 selected from adenosine or deoxyadenosine; or when the pairing nucleotide in the target RNA is uridine, adenosine in position 1 of the antisense strand is substituted with an N 1 which is deoxyuridine; wherein z" may be present or absent, but if present is a capping moiety covalently attached at the 5' terminus of N 2 -(N')y; and wherein each of Z and Z' is independently present or absent, but if present is independently 1-5 consecutive nucleotides, consecutive non-nucleotide moieties or a combination thereof covalently attached at the 3' terminus of the strand in which it is present.