Ligase chain reaction with endonuclease IV correction and contamination control

In a ligase chain reaction method for amplifying a target nucleic acid sequence, said method including:

• (a) providing at least two sets of two probes, the 3' end of an upstream probe being ligated to the 5' end of a downstream probe in the presence of target to form a primary ligation product and the second set of probes hybridizing to the primary ligation product and being ligated to each other to form a secondary ligation product;
• (b) repeatedly denaturing the hybridized strands, reannealing additional probes and ligating them;
• and (c) detecting to what extent ligation products have formed, the improvement comprising:
• (a) providing in at least one of the upstream probes a 3' end modification such that the probe is incapable of ligation to its downstream partner, said 3' end modification being correctable substantially only when the modified probe is hybridized to the target sequence;
• (b) hybridizing the modified probe to the target, if present, to form a modified probe-template complex;
• (c) correcting the modification in a target dependent manner using endonuclease IV activity to create a 3' hydroxyl end, thus allowing the corrected probe to be ligated to its downstream partner;
• (d) ligating the corrected probe to its downstream partner to form an amplification product;
• and
• (e) dissociating the amplification product from the target and repeating the hybridization, correction and ligating steps to amplify the desired target sequence.