Double-stranded nucleic acid complex having overhang
View Patent ↗Provided is a nucleic acid strand that can efficiently deliver an antisense oligonucleotide into the body, particularly a nucleic acid complex comprising a first nucleic acid strand and a second nucleic acid strand, wherein the first nucleic acid strand includes a base sequence that is capable of hybridizing with at least a portion of a target transcription product, and exerts an antisense effect on the target transcription product; the second nucleic acid strand includes a complementary region having a base sequence complementary to the first nucleic acid strand and at least one overhang region located on the 5′ and/or 3′ side of the complementary region; and the first nucleic acid strand is annealed to the complementary region in the second nucleic acid strand.
1. A nucleic acid complex comprising a first nucleic acid strand and a second nucleic acid strand,
wherein the first nucleic acid strand comprises a base sequence that is capable of hybridizing with at least part of a target transcription product;
wherein the first nucleic acid strand has an antisense effect on the target transcription product;
wherein the first nucleic acid strand is 13 to 20 bases in length;
wherein the second nucleic acid strand comprises a complementary region comprising a base sequence complementary to the first nucleic acid strand and at least one overhang region located on the 5′ terminal and/or 3′ terminal side of the complementary region;
wherein the overhang region in the second nucleic acid strand does not have an ability to substantially hybridize to transcription products in a cell and does not influence gene expression;
wherein the first nucleic acid strand is annealed to the complementary region in the second nucleic acid strand, and
wherein the first nucleic acid strand comprises a peptide nucleic acid and/or a morpholino nucleic acid.
2. The nucleic acid complex according to claim 1 , wherein the second nucleic acid strand further comprises a functional moiety having a function selected from a labeling function, a purification function, and a target delivery function.
3. The nucleic acid complex according to claim 1 , wherein the complementary region in the second nucleic acid strand does not comprise at least two consecutive ribonucleosides.
4. A nucleic acid complex comprising a first nucleic acid strand and a second nucleic acid strand,
wherein the first nucleic acid strand comprises a base sequence that is capable of hybridizing with at least part of a target transcription product;
wherein the first nucleic acid strand has an antisense effect on the target transcription product;
wherein the first nucleic acid strand is 13 to 20 bases in length;
wherein the second nucleic acid strand comprises a complementary region comprising a base sequence complementary to the first nucleic acid strand and at least one overhang region located on the 5′ terminal and/or 3′ terminal side of the complementary region;
wherein the overhang region in the second nucleic acid strand does not have an ability to substantially hybridize to transcription products in a cell and does not influence gene expression;
wherein the first nucleic acid strand is annealed to the complementary region in the second nucleic acid strand, and
wherein the overhang region in the second nucleic acid strand comprises a modified nucleoside comprising a bicyclic sugar and is at least bases in length.
5. The nucleic acid complex according to claim 1 , wherein the overhang region in the second nucleic acid strand does not comprise a modified nucleoside comprising a bicyclic sugar and is 9 to 17 bases in length.
6. A composition comprising the nucleic acid complex according to claim 1 , and a pharmaceutically acceptable carrier.
7. The composition according to claim 6 , wherein the composition is for intravenous administration, intraventricular administration, intrathecal administration, intramuscular injection administration, continuous infusion administration, intraperitoneal administration, inhalation, skin patch, or subcutaneous administration.
8. The nucleic acid complex according to claim 4 , wherein at least one internucleoside linkage from the free end of the overhang region in the second nucleic acid strand is a modified internucleoside linkage.
9. The nucleic acid complex according to claim 4 , wherein at least 50% of the internucleoside linkages within the overhang region in the second nucleic acid strand are modified internucleoside linkages.
10. The nucleic acid complex according to claim 9 , wherein the modified internucleoside linkage is a phosphorothioate linkage.
11. The nucleic acid complex according to claim 1 , wherein at least one nucleoside from the free end of the overhang region in the second nucleic acid strand is a modified nucleoside.
12. The nucleic acid complex according to claim 11 , wherein the modified nucleoside comprises a bicyclic sugar.