Development of a novel pretargeting system with bifunctional nucleic acid molecules.

This study was aimed at exploring a novel pretargeting system based upon bifunctional nucleic acid molecules that are comprised of a nucleic acid aptamer and a nucleic acid tail. The properties of bifunctional molecules were investigated by both theoretical prediction and experimental determination. Different from the algorithm-based structure prediction, the experimental data showed that some nucleic acid tails could significantly decrease the binding capability of the aptamer. It was also found that the effectiveness of bifunctional molecules in labeling cells was dependent on the hybridization length. Based on these understandings, one bifunctional molecule was selected to study pretargeting. The results demonstrated that the bifunctional molecule could not only bind to target cells, but also hybridize with its complementary oligonucleotide on the cell surface. Thus, bifunctional nucleic acid molecules hold great potential for pretargeting applications.