This laboratory is developing sequence-specific DNA analogs against cancer genes and neurological genes for use as diagnostics and therapeutics. The cancer gene mRNAs being studied include CCND1, MYCC, HER2, IGF1R, and KRAS2 in breast cancer, colon cancer, lung cancer, pancreatic cancer, and prostate cancer. In a new direction, we have begun to knock down two microRNAs, miR-17 and miR-21, which are overexpressed in triple negative breast cancer cells. Micro RNA precursor duplexes were thought to include an active guide strand and an inactive passenger strand. However, we discovered passenger strand activity in triple negative breast cancer cells, when anti-miR-17-5p depressed PTEN and PDCD4 protein, instead of raising them. Nuclease-resistant sequences that specifically block miR-17 or miR-21 might interdict triple negative breast cancer cell growth. To see active cancer gene mRNAs from outside the body, we synthesize peptide analogs that enable receptor-specific uptake and mRNA hybridization of peptide nucleic acids (PNA). By adding a radionuclide chelator to one end of a PNA-peptide, we radio image cancerous or precancerous regions by single photon emission computed tomography (SPECT) or positron emission tomography (PET).
microRNA Blockade to Induce Immune Response in Triple Negative Breast Cancer
Fig. 1. (after microRNA project title) We simulated all predicted 3’-UTR mRNA:oncomiR duplexes, for both guide strands and passenger strands. We calculated 25 ns accelerated molecular dynamics of each duplex in explicit H2O with 100 mM NaCl at 300K with AMBER 12. Blue spheres represent Na+. Our molecular dynamics calculations predicted stable A-form duplexes for all oncomiR passenger strand:mRNA targets, as well as for guide strands. Thus, 3’-UTR mRNA:oncomiR duplexes can be accommodated in the substrate groove of Ago2.
Non-Small Cell Lung Cancer Treatment Monitoring by Genomic Imaging
Fig. 2. (after Non-Small Lung Cancer project) KRAS PET imaging of [64Cu]KRAS G12D agent in spontaneous lung lesion of a transgenic KRAS G12D mouse, showing strong SUV.
VPAC1 Receptor-Targeted PET Imaging of Prostate Cancer
Fig. 3. (after Prostate project) Volumetric 3D rendering of VPAC1+ prostate lesions (red) from fusion of VPAC1 [64Cu]peptide PET image with CT.
Capture, Isolation, Enumeration, and Classification of Breast Cancer Cells in Blood
Fig. 4. (after Capture project) Blood samples being applied to 76-element antibody-nanotube microelectrode array for instantaneous droplet biopsy.