The SNAP System

Abstract

Since their advent, the use of synthetic nucleic acid probes for detection of nucleotide sequences has offered specificity and handling advantages over cloned DNA probes. Highly specific oligonucleotides can distinguish between sequences with as few as one nucleotide difference (Wallace et al., 1979). Automated chemistry has enabled the routine production of high purity oligonucleotides using phosphoamidite chemistry. The development of SNAP (synthetic nucleic acid probe; SNAP is a registered trademark of Syngene, Inc.) technology has provided a safe and convenient method for labeling these oligomer probes and detecting their targets (Ruth et al., 1985; Fig. 1). The SNAP system uses synthetic oligonucleotides which have been covalently coupled to a nonisotopic reporter molecule, most typically alkaline phosphatase (AP). Addition of AP substrates to these conjugated oligomers (AP probes) results in the enzymatic production of a detectable signal (Jablonski et al., 1986; Ruth and Jablonski, 1987). Similar to unconjugated oligomers, AP-labeled probes show the same high degree of specificity achievable with radioactively labeled oligomer probes (Podell et al., 1991). Unlike isotopically labeled probes, these enzyme-labeled probes are more sensitive and show remarkable stability.