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 strand comprising, sequentially, a first, second and third fragments and defined as S-Q-P, wherein each letter denotes a fragment and a string of letters connected by “-” denotes a strand, and (ii) a second strand comprising, sequentially, a first, second, third and fourth fragments and defined as A- B - P - Q , wherein the first complex comprises a duplex region (Q-P:: P - Q ) formed between the second and third fragments of the first strand and the third and fourth fragments of the second 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 P-B- Ā, (ii) a second nucleic acid strand comprising, sequentially, a first, second and third fragments and defined as A-X-C, and (iii) a third strand comprising, sequentially, a first, second and third fragments and defined as D - X - B , wherein the second complex comprises a first duplex region (Ā::A) formed between the third fragment of the first strand and the first fragment of the second strand, a second duplex region (B:: B ) formed between the first fragment of the first strand and the third fragment of the third strand, and a third duplex region (X:: X ) formed between the second fragment of the second strand and the second fragment of the third strand,
wherein the first (S) fragment of the first strand of the first complex, the first (A) and second ( B ) of the second strand of the first complex, the first fragment (P) of the third strand of the second complex, the third fragment (C) of the second strand of the second complex, and the first fragment ( D ) of the third strand of the second complex are single-stranded; and
wherein the first, second and third fragments (A, B , P ) of the second strand of the first complex have sequence complementarity to the third, second and first fragments (Ā, B, P) of the first strand of the second complex to allow binding therebetween, respectively.
2. The composition of claim 1 , wherein the first strand (S-Q-P) of the first complex has sequence complementarity to a fragment on a nucleic acid of a pathogenic nucleic acid to allow binding therebetween.
3. The composition of claim 2 , wherein the pathogenic nucleic acid is a viral DNA, a viral RNA, a bacterial DNA, a bacterial RNA, a mutant tumor DNA, or a tumor RNA.
4. The composition of claim 1 , wherein each fragment is from about 5 bases to about 50 bases long.
5. The composition of claim 1 , wherein each fragment that is single-stranded is from about 5 bases to about 30 bases long.
6. The composition of claim 1 , further comprising a pharmaceutically acceptable carrier.