Rotationally sequestered translators
Provided are nucleic acid translators capable of carrying out logic operations with improved efficiency, maximized output and reduced off-target effects, in particular in a biological system. Methods of using these translators to transduce signal are also provided.
1. A composition comprising a first nucleic acid complex comprising (a) a first, a second, a third and a fourth nucleic acid strands each comprising, sequentially, a first, a second and a third fragments and (b) a first and second RNA strands, wherein the first complex comprises:
(i) a first duplex region formed between the second fragments of the first and second strands;
(ii) a second duplex region formed between the second fragments of the third and fourth strands;
(iii) a third duplex region formed between the third fragment of the first strand and the first fragment of the third strand;
(iv) a fourth duplex region formed between the first fragment of the second strand and the third fragment of the fourth strand;
(v) a fifth duplex region formed between the third fragment of the third strand and the first RNA; and
(vi) a sixth duplex region formed between the first fragment of the fourth strand and the second RNA,
and the first fragment ( C ) of the first strand and the third fragment (D) of the second strand are single-stranded.
2. The composition of claim 1 , further comprising a second nucleic acid complex comprising a first and a second nucleic strands and a first and a second RNA strands, wherein:
the second complex comprises a first duplex region formed between the second fragments of the first and second strands, a second duplex region formed between the third fragment of the first strand and the first RNA strand, and a third duplex region formed between the first fragment of the second strand and the second RNA strand, wherein the first fragment (E) of the first strand and the third fragment ( F ) of the second strand are single-stranded;
the third strand of the first complex and the second strand of the second complex have sequence complementarity to allow binding therebetween; and
the fourth strand of the first complex and the first strand of the second complex have sequence complementarity to allow binding therebetween.
3. The composition of claim 1 , wherein each fragment is from about 5 bases to about 50 bases long.
4. The composition of claim 1 , wherein each fragment that is single-stranded is from about 5 bases to about 30 bases long.
5. The composition of claim 1 , further comprising a pharmaceutically acceptable carrier.
6. A nucleic acid complex comprising a first, a second, a third, a fourth, a fifth and a sixth nucleic acid strands, wherein:
the first strand comprises, sequentially, a first, a second, a third and a fourth fragments and is defined as Q - X - B -Ā, wherein each letter denotes a fragment and a string of letters connected by “-” denotes a strand;
the second strand comprises, sequentially, a first, a second, a third and a fourth fragments and is defined as B -Ā- X -P;
the third and fifth strands each comprises, sequentially, a first, a second and a third fragments and is defined as A-Y-C; and
the fourth and sixth strands each comprises, sequentially, a first, a second and a third fragments and is defined as D - Y -B;
and wherein the complex comprises:
a first duplex region ( X :X) formed between the second fragment of the first strand and the third strand of the second strand;
a second duplex region (Ā::A) formed between the fourth fragment of the first strand and the first strand of the third strand;
a third duplex region ( B ::B) formed between the third fragment of the first strand and the third fragment of the fourth strand;
a fourth duplex region (Ā::A) formed between the second fragment of the second strand and the first fragment of the fifth strand;
a fifth duplex region ( B ::B) formed between the first fragment of the second strand and the third fragment of the sixth strand;
a sixth duplex region (Y:: Y ) formed between the second fragments of the third and fourth strands; and
a seventh duplex region (Y:: Y ) formed between the second fragments of the fifth and sixth strands,
and wherein the first fragment ( Q ) of the first strand, the fourth fragment (P) of the second strand, the third fragments (C) of the third and fifth strands and the first fragments ( D ) of the fourth and sixth strands are single-stranded.
7. The composition of claim 6 , wherein each fragment is from about 5 bases to about 50 bases long.
8. The composition of claim 6 , wherein each fragment that is single-stranded is from about 5 bases to about 30 bases long.
9. The composition of claim 6 , further comprising a pharmaceutically acceptable carrier.