A highly sensitive method was developed by Overhoff et al. [176] for the detection of siRNA after phosphorothioatestimulated uptake [177] and adapted for the quantification of siRNA or steric block oligonucleotides after non-covalent peptide-mediated delivery ( [55] and Laufer et al., manuscript in preparation, see chapter "MPG -mediated delivery of siRNA and steric block oligonucleotides"). This so-called liquid hybridization assay is based on the extraction of total cellular RNA and the subsequent hybridization in solution of a radioactively labeled probe which is complementary to the oligonucleotide to be detected. Finally, following PAGE analysis, absolute amounts of internalized oligonucleotide can be quantified with high accuracy down to ~10 molecules per cell using internal standards [55] . In addition to this outstanding sensitivity, no amplification step is needed and only intact oligonucleotides are taken into account.