A short interfering nucleic acid (siNA) molecule capable of mediating RNA interference comprising an antisense strand that is complementary to a nucleic acid target, wherein said antisense strand comprises a 5' modified nucleotide having Formula II: wherein: A is -OCH 2 -, -CH 2 CH 2 - or -CH=CH-; B is any heterocyclic base moiety; D 1 and D 1' are independently selected from hydroxyl, -OCH 3 or -OCH 2 CH 3; E is O; J is a phosphodiester internucleoside linking group or a phosphorothioate internucleoside linking group linking the 5' modified nucleotide of Formula II to the sugar moiety of an adjacent nucleotide of the siNA molecule; R 1 is H or hydroxyl, and R 1' is H, hydroxyl, halogen or -OR 6; R 2 is H, C 1-6 alkyl or C 2-6 alkenyl; R 6 is independently selected from H, C 1-6 alkyl (which is optionally substituted with -OR 7, -SR 7, -N(R 8) 2, or (=O)-NR 9 or from one to three halogen), C 2-6 alkenyl, C 2-6 alkynyl, aryl, wherein R' is selected from H or C 1-4 alkyl (which is optionally substituted with one to three substituents independently selected from -SR 10, aryl, heteroaryl, amino, hydroxyl, oxo, -NH-C= NH 2, wherein the aryl and heteroaryl are optionally substituted with hydroxyl), and R" is selected from H, C 1-18 alkyl or aryl; R 7 is methyl, -CF 3, -N(R 8) 2 or -CH 2 -N(R 8) 2; R 8 is independently selected from H or C 1-6 alkyl; R 9 is (R 8) 2, -R 8 -(CH 2) 2 -N(R 8) 2 or -R 8 -C(=NR 8)[N(R 8) 2]; and R 10 is H or C 1-4 alkyl; wherein the siNA molecule is a single-stranded antisense molecule, or wherein the siNA molecule is a double-stranded molecule comprising a sense strand that is complementary to the antisense strand and wherein the single-stranded molecule is between 15 and 30 nucleotides in length, or wherein the antisense strand and the sense strand are each independently 15 to 30 nucleotides in length. A is -OCH 2 -, -CH 2 CH 2 - or -CH=CH-; B is any heterocyclic base moiety; D 1 and D 1' are independently selected from hydroxyl, -OCH 3 or -OCH 2 CH 3; E is O; J is a phosphodiester internucleoside linking group or a phosphorothioate internucleoside linking group linking the 5' modified nucleotide of Formula II to the sugar moiety of an adjacent nucleotide of the siNA molecule; R 1 is H or hydroxyl, and R 1' is H, hydroxyl, halogen or -OR 6; R 2 is H, C 1-6 alkyl or C 2-6 alkenyl; R 6 is independently selected from H, C 1-6 alkyl (which is optionally substituted with -OR 7, -SR 7, -N(R 8) 2, or (=O)-NR 9 or from one to three halogen), C 2-6 alkenyl, C 2-6 alkynyl, aryl, wherein R' is selected from H or C 1-4 alkyl (which is optionally substituted with one to three substituents independently selected from -SR 10, aryl, heteroaryl, amino, hydroxyl, oxo, -NH-C= NH 2, wherein the aryl and heteroaryl are optionally substituted with hydroxyl), and R" is selected from H, C 1-18 alkyl or aryl; R 7 is methyl, -CF 3, -N(R 8) 2 or -CH 2 -N(R 8) 2; R 8 is independently selected from H or C 1-6 alkyl; R 9 is (R 8) 2, -R 8 -(CH 2) 2 -N(R 8) 2 or -R 8 -C(=NR 8)[N(R 8) 2]; and R 10 is H or C 1-4 alkyl; wherein the siNA molecule is a single-stranded antisense molecule, or wherein the siNA molecule is a double-stranded molecule comprising a sense strand that is complementary to the antisense strand and wherein the single-stranded molecule is between 15 and 30 nucleotides in length, or wherein the antisense strand and the sense strand are each independently 15 to 30 nucleotides in length.