One challenge in working with a family of homologous genes is finding a reagent that can silence one gene without acting on its brethren. This is a question of specificity, and Active Motif of Carlsbad, Calif., claims its gripNA™ probes are more specific than conventional antisense oligonucleotide reagents and more effective than the peptide nucleic acids (PNAs) from which gripNAs derive.
Although PNAs exhibit strong hybridization and specificity properties, they tend to aggregate, limiting their use in vivo. The gripNAs posses a negatively charged backbone that increases solubility, yet they retain PNAs benefits, including nuclease resistance and strong sequence specificity. "They don't tolerate mismatches well," says John Archdeacon, research and development manager, citing experiments that compare the binding strengths of gripNA and DNA probes to complementary sequences. The presence of a single-base mismatch in the target sequence either prevents or destabilizes duplex formation by the gripNA probe.
Biochemist Gilles Divita, ...
