Targeted PMP22 TATA-box editing by CRISPR/Cas9 reduces demyelinating neuropathy of Charcot-Marie-Tooth disease type 1A in mice.

Charcot-Marie-Tooth 1A (CMT1A) is the most common inherited neuropathy without a known therapy, which is caused by a 1.4 Mb duplication on human chromosome 17, which includes the gene encoding the peripheral myelin protein of 22 kDa (PMP22). Overexpressed PMP22 protein from its gene duplication is thought to cause demyelination and subsequently axonal degeneration in the peripheral nervous system (PNS). Here, we targeted TATA-box of human PMP22 promoter to normalize overexpressed PMP22 level in C22 mice, a mouse model of CMT1A harboring multiple copies of human PMP22. Direct local intraneural delivery of CRISPR/Cas9 designed to target TATA-box of PMP22 before the onset of disease, downregulates gene expression of PMP22 and preserves both myelin and axons. Notably, the same approach was effective in partial rescue of demyelination even after the onset of disease. Collectively, our data present a proof-of-concept that CRISPR/Cas9-mediated targeting of TATA-box can be utilized to treat CMT1A.

Silicon-nitride microring resonators for nonlinear optical and biosensing applications.

We discuss the design, fabrication, and characterization of silicon-nitride microring resonators for nonlinear-photonic and biosensing device applications. The first part presents new theoretical and experimental results that overcome highly normal dispersion of silicon-nitride microresonators by adding a dispersive coupler. The latter parts review our work on highly efficient second-order nonlinear interaction in a hybrid silicon-nitride slot waveguide with nonlinear polymer cladding and silicon-nitride microring application as a biosensor for human stress indicator neuropeptide Y at the nanomolar level.

Quantification of Neuropeptide Y with Picomolar Sensitivity Enabled by Guided-Mode Resonance Biosensors.

Assessing levels of neuropeptide Y (NPY) in the human body has many medical uses. Accordingly, we report the quantitative detection of NPY biomarkers applying guided-mode resonance (GMR) biosensor methodology. The label-free sensor operates in the near-infrared spectral region exhibiting distinctive resonance signatures. The interaction of NPY with bioselective molecules on the sensor surface causes spectral shifts that directly identify the binding event without additional processing. In the experiments described here, NPY antibodies are attached to the sensor surface to impart specificity during operation. For the low concentrations of NPY of interest, we apply a sandwich NPY assay in which the sensor-linked anti-NPY molecule binds with NPY that subsequently binds with anti-NPY to close the sandwich. The sandwich assay achieves a detection limit of ~0.1 pM NPY. The photonic sensor methodology applied here enables expeditious high-throughput data acquisition with high sensitivity and specificity. The entire bioreaction is recorded as a function of time, in contrast to label-based methods with single-point detection. The convenient methodology and results reported are significant, as the NPY detection range of 0.1-10 pM demonstrated is useful in important medical circumstances.

Resonant grating polarizers made with silicon nitride, titanium dioxide, and silicon: design, fabrication, and characterization.

We present the design, fabrication, and characterization of guided-mode resonance (GMR) linear polarizers that operate in the optical communications C-band near a wavelength of 1550 nm. We provide theoretical and experimental spectra using resonant elements fashioned in three material systems. In particular, we investigate silicon nitride resonant gratings and titanium dioxide gratings on glass substrates as well as silicon-on-quartz gratings. These materials exhibit very low losses and are capable of high diffraction efficiencies and extinction ratios; thus, high-power laser applications may be enabled. We present the methods applied to fabricate these GMR devices as well as means to ascertain their fabricated physical parameters. We quantify increased polarizer bandwidth with increased grating refractive-index modulation. The numerical results obtained with the fabricated-device parameters agree well with the experimental measured spectra.

Optical filters fabricated in hybrimer media with soft lithography.

Fabrication and characterization of guided-mode resonance filters made by soft lithography are presented. As these resonant elements are highly sensitive to parametric variations, it is important to develop methods for their reliable fabrication. Thus, we provide a fabrication process that is consistent and simple, employing an elastomeric mold and a UV-curable organic-inorganic hybrid material. Measured spectra show approximately 81% reflectance and approximately 8% transmittance at a resonance wavelength of 1538 nm. The filter's linewidth is approximately 4.5 nm, and the sideband reflectance is approximately 5%. Experimental and theoretical results are in good agreement.