- Brain Awareness Week
RNA Based Therapeutics Targeting the Nervous System
My research is primarily focused on nucleic acid-based diagnostic technologies for infectious diseases.
With a simple quenched fluorescent oligonucleotide probe format (see Figure), my research group can rapidly and selectively detect the presence of a variety of bacterial pathogens via the unique properties of their nucleases. By identifying an appropriate oligonucleotide sequence and chemical composition, we tailor each probe to be specifically activated by a target nuclease. Chemically modified nucleotides are used to facilitate resistance to non-target nucleases. For instance, oligonucleotides composed of 2¢-O-methyl or 2¢-fluoro modified nucleotides are known to be resistant to degradation by mammalian serum nucleases, but we found that some bacterial nucleases can efficiently digest them. We have engineered chemically modified oligonucleotide probes to be specifically activated by nucleases of Mycoplasma fermentans (see Hernandez et al., Nucleic Acid Therapeutics, 2012), Staphylococcus aureus (see Hernandez et al., Nature Medicine, 2014) and Escherichia coli (unpublished). Due to their simplicity of use, and high sensitivity and specificity, these probes may be used to address a variety of unmet clinical needs. With the S. aureus-specific probe, we developed a proof-of-concept study in which we demonstrated the rapid, non-invasive imaging of focal S. aureus infections in mice (see Hernandez et al., Nature Medicine, 2014). Ongoing projects include efforts to translate the probe-based S. aureus detection to clinical practice and to evaluate the potential of E. coli specific probes for various clinical diagnostic endpoints.