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.

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.

Broadband polarization rotator based on multi-order plasmon resonances and high impedance surfacesWe present the design, fabrication, and characterization of a guided-mode resonance polarizer operating in the telecommunication band. This polarizer consists of a single one-dimensional silicon grating layer and a glass substrate. The device is designed using inverse mathematical methods and fabricated by thin-film deposition, holographic-interference patterning, and etching. The fabricated polarizer has high transmittance for transverse-magnetic polarization and low transmittance for transverse-electric polarization over a ϳ200 nm wavelength range. Its experimental extinction ratio is ϳ670: 1 at a central wavelength c = 1563 nm. Experimental and theoretical results are in good agreement.

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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.