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) a first nucleic acid complex comprising (i) a first nucleic acid strand comprising, sequentially, a first, second and third fragments and defined as B-X-D, (ii) a second nucleic acid strand comprising, sequentially, a first, second and third fragments and defined as C - X -Ā, (iii) a third strand comprising, sequentially, a first, second and third fragments and defined as D - Y -Ē, and (iv) a fourth strand comprising, sequentially, a first, second and third fragments and defined as F-Y-C, wherein the first complex comprises a first duplex region (X:: X ) 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; and
(b) a second nucleic acid complex comprising (i) a first nucleic acid strand comprising, sequentially, a first, second and third fragments and defined as C - Y - F , (ii) a second nucleic acid strand comprising, sequentially, a first, second and third fragments and defined as E-Y-D, (iii) a third strand comprising, sequentially, a first and second fragments and defined as F-Z, and (iv) a fourth strand comprising, sequentially, a first and second fragments and defined as Z -Ē, wherein the second 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 fragment of the third strand and the first fragment of the fourth strand, a third duplex region ( F ::F) formed between the third fragment of the first strand and the first fragment of the third strand, and a fourth duplex region (E::Ē) formed between the first fragment of the second strand and the second fragment of the fourth strand,
wherein the first (B) fragment of the first strand, the third fragment (Ā) of the second strand, the third fragment (Ē) of the third strand, and the first fragment (F) of the fourth strand of the first complex, and the first ( C ) fragment of the first strand and the third fragment of the second strand (D) of the second complex are single-stranded;
wherein the first, second and third fragments ( D , Y , and Ē) of the third strand of the first complex have sequence complementarity to the third, second and first fragments (D, Y, and E) of the second strand of the second complex to allow binding therebetween, respectively; and
wherein the third, second and first fragments (C, Y, and F) of the fourth strand of the first complex have suitable sequence complementarity to the first, second and third fragments ( C , Y , and F ) of the first strand of the second complex to allow binding therebetween, respectively.
2. The composition of claim 1 , wherein the first fragment (F) of the fourth strand of the first complex is at least 5 nucleotides (nt) longer than the third fragment (Ē) of the third strand of the first complex.
3. The composition of claim 1 , wherein the first fragment ( Z ) of the fourth strand of the second complex is at least 30 nucleotides (nt) long.