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, a second and a third nucleic acid complexes, wherein:
the first complex comprises a first, a second, a third and a fourth nucleic acid strands each comprising, sequentially, a first, a second and a third fragments and defined as B-W-D, C - W -Ā, D - Y -H, and G -Y-C, respectively, wherein each letter denotes a fragment and each string of letters connected by “-” denotes a strand, and wherein the first complex comprises a first duplex region (W:: W ) formed between the second fragments of the first and second strands, a second duplex region ( Y ::Y) formed between the second fragments of the third and fourth strands, a third duplex region (D:: D ) formed between the third fragment of the first strand and the first fragment of the third strand; and a fourth duplex region ( C ::C) formed between the first fragment of the second strand and the third fragment of the fourth strand;
the second complex comprises a first, a second, a third and a fourth nucleic acid strands each comprising, sequentially, a first, a second and a third fragments and defined as F-X-H, G - X -Ē, H - Z -Ī and J-Z-G, respectively, wherein the second complex comprises a first duplex region (X:: X ) formed between the second fragments of the first and second strands, a second duplex region ( Z ::Z) formed between the second fragments of the third and fourth strands, a third duplex region (H:: H ) formed between the third fragment of the first strand and the first fragment of the third strand; and a fourth duplex region ( G ::G) formed between the first fragment of the second strand and the third fragment of the fourth strand;
the third complex comprises a first, a second, a third, a fourth, a fifth and a sixth nucleic acid strands each comprising, sequentially, a first, a second and a third fragments and defined as C - Y -G, H -Y-D, G - Z - J , I-Z-H, J-Q-M and N - Q -Ī, respectively, wherein the third complex comprises a first duplex region ( Y ::Y) formed between the second fragments of the first and second strands, a second duplex region ( Z ::Z) formed between the second fragments of the third and fourth strands, a third duplex region (Q:: Q ) formed between the second fragments of the fifth and sixth strands, a fourth duplex region (G:: G ) formed between the third fragment of the first strand and the first fragment of the third strand; a fifth duplex region ( H ::H) formed between the first fragment of the second strand and the third fragment of the fourth strand, a sixth duplex region ( J ::J) formed between the third fragment of the third strand and the first fragment of the fifth strand, and a seventh duplex region (I::Ī) formed between the first fragment of the fourth strand and the third fragment of the sixth strand;
wherein, in the first complex, the first fragment (B) of the first strand, the third fragment (Ā) of the second fragment, the third fragment (H) of the third strand, and the first fragment ( G ) of the fourth strand are single-stranded; in the second complex, the first fragment (F) of the first strand, the third fragment (Ē) of the second fragment, the third fragment (Ī) of the third strand, and the first fragment (J) of the fourth strand are single-stranded; and in the third complex, the first fragment ( C ) of the first strand, the third (D) fragment of the second strand, the third fragment (M) of the fifth fragment, and the first fragment ( N ) of the sixth strand are single-stranded,
and wherein:
the third strand ( D - Y -H) of the first complex and the second strand ( H -Y-D) of the third complex have sequence complementarity to allow binding therebetween;
the fourth strand ( G -Y-C) of the first complex and the first strand ( C -Y-G,) of the third complex have sequence complementarity to allow binding therebetween;
the third strand ( H - Z -Ī) of the second complex and the fourth strand (I-Z-H) of the third complex have sequence complementarity to allow binding therebetween; and
the fourth strand (J-Z-G) of the second complex and the third strand ( G - Z -Ĵ) of the third complex have sequence complementarity to allow binding therebetween.
2. The composition of claim 1 , wherein each fragment is from about 5 bases to about 50 bases long.
3. The composition of claim 1 , wherein each fragment that is single-stranded is from about 5 bases to about 30 bases long.
4. The composition of claim 1 , further comprising a pharmaceutically acceptable carrier.
5. A cell comprising the composition of claim 1 .