Self-neutralizing oligonucleotides with enhanced cellular uptake.

There is tremendous potential for oligonucleotide (ON) therapeutics, but low cellular penetration due to their polyanionic nature is a major obstacle. We addressed this problem by developing a new approach for ON charge neutralization in which multiple branched charge-neutralizing sleeves (BCNSs) are attached to the internucleoside phosphates of ON by phosphotriester bonds. The BCNSs are terminated with positively charged amino groups, and are optimized to form ion pairs with the neighboring phosphate groups.

Direct detection of the bacterial stress response in intact samples of platelets by differential impedance.

Background: We have previously described a new rapid approach that relies on monitoring intentionally stressed bacteria in contaminated platelet concentrates (PCs). This earlier work included human cell lysis with Triton X-100 and filtration as steps in the sample preparation. This study was undertaken to develop an improved and time-saving protocol that enables direct bacterial detection in PCs without lysis and filtration.

Rapid microbiological testing: monitoring the development of bacterial stress.

The ability to respond to adverse environments effectively along with the ability to reproduce are sine qua non conditions for all sustainable cellular forms of life. Given the availability of an appropriate sensing modality, the ubiquity and immediacy of the stress response could form the basis for a new approach for rapid biological testing. We have found that measuring the dielectric permittivity of a cellular suspension, an easily measurable electronic property, is an effective way to monitor the response of bacterial cells to adverse conditions continuously.

New approach for drug susceptibility testing: monitoring the stress response of mycobacteria.

Methods currently used for in vitro drug susceptibility testing are based on the assessment of bacterial growth-related processes. This reliance on cellular reproduction leads to prolonged incubation times, particularly for slowly growing organisms such as mycobacteria. A new rapid phenotypic method for the drug susceptibility testing of mycobacteria is described.

Monitoring the physiologic stress response: a novel biophysical approach for the rapid detection of bacteria in platelet concentrate.

Background: Currently approved culture-based methods for the bacterial testing of platelet concentrates (PCs) require an extended period of time to obtain results. A new approach based on the monitoring of the bacterial response to physiologic stress is presented. Because the stress response is independent of the growth rate, decisive results can be obtained in near real time.