This Small Business Innovation Research (SBIR) Phase I research project aims to develop novel nucleic acid labeling reagents that can be used in living cells to monitor gene expression. Instead of relying on labeling the molecules using fluorescently labeled bases, the proposed approach relies on adding the label to the terminal phosphates. This would have great advantage over existing methods and would be a welcome addition to the tools of molecular analysis.<br/><br/>Current detection of the changes in gene expression relies on the labeling of nucleic acids with fluorescent labels, which sometimes interferes with hybridization. Thus development of a technology that allows labeling of the nucleic acids in such a way so as to not affect the molecules? hybridization parameters would be a significant advance. Moreover, such a technology would make quantitiation of the hybridization event easier as the fluorescence intensity of the probe molecules would not be sequence dependent. In addition, the obviation of the need for enzyme incorporation and amplification methods would reduce the time and cost associated with the labeling of probes.