Systems and uses thereof for creating synthetic transcriptional logic ‘and’ gates based on pre-mRNA trans-splicing

A synthetic nucleic acid expression system for production of a transcript of interest in a cell-state, the system comprising,

• a) a first nucleic acid sequence comprising a first promoter operably linked to a nucleic acid sequence encoding a first trans-spliceable pre-mRNA sequence comprising at least one exon encoding a 5′ fragment of said transcript of interest and a first RNA sequence required for spliceosome-dependent trans-splicing, wherein said first RNA sequence required for spliceosome-dependent trans-splicing comprises a donor site for splicing and a first hybridization sequence;
• and
• b) a second nucleic acid sequence comprising a second promoter operably linked to a nucleic acid sequence encoding a second trans-spliceable pre-mRNA sequence comprising at least one exon encoding a 3′ fragment of said transcript of interest and a second RNA sequence required for spliceosome-dependent trans-splicing wherein said first RNA sequence required for spliceosome-dependent trans-splicing comprises an acceptor site for splicing and a second hybridization sequence;
• wherein said first promoter and said second promoter are different and each one is active in said cell-state,
• wherein said first hybridization sequence is complementary to said second hybridization sequence, and wherein said first and said second hybridization sequences lack 100% base complementarity with each transcript of the innate transcriptome of said cell-state,
• and each one of said at least one exons encodes an incomplete transcript of interest, and a messenger RNA comprising said at least one exon encoding a 5′ fragment of said transcript of interest joined to said at least one exon encoding a 3′ fragment of said transcript of interest encodes a complete transcript of interest.