Abstract: The present invention relates to Charcot-Marie-Tooth disease 2A (CMT2A) harboring the p.Arg364Trp or p.His361Tyr Mfn2 mutation, whose human counterpart results in severe, early-onset axonal neuropathy for p.Arg364Trp Mfn2 mutation in fertilized rat eggs. Cohorts of mutants and wild type littermates were characterized with multiple motor deficits that worsened over time. Separate cohorts of mutant and wild type at 7, 40, and 48 weeks showed reduced density of myelinated axons and active axonal degeneration in distal but not proximal nerves, as well as axonal degeneration in the fasciculus gracilis of the cervical spinal cord at 40 and 48 weeks not present in 7-week-old cohort Mfn2 mutants, or wild type at 7 or 40 weeks. The p.His361Tyr Mfn2 mutation using CRISPR/Cas9 showed abnormalities in gait dynamics at 8 weeks and lengthening of gait cycle at 16 weeks. The invention provides progressive axonal neuropathy for examining pathogenesis and treatment of CMT2A.

Abstract: This invention provides RNA, oligoribonucleotide, and polyribonucleotide molecules comprising pseudouridine or a modified nucleoside, gene therapy vectors comprising same, methods of synthesizing same, and methods for gene replacement, gene therapy, gene transcription silencing, and the delivery of therapeutic proteins to tissue in vivo, comprising the molecules. The present invention also provides methods of reducing the immunogenicity of RNA, oligoribonucleotide, and polyribonucleotide molecules.

Abstract: Provided herein are methods, systems and apparatus for diagnosing, predicting and/or preventing acute allograft vasculopathy in an organ transplant patient. The method comprises executing on a processor the steps comprising: analyzing clinical risk factors of a cardiac, kidney or liver transplant patient in a model which distinguishes between clinical biomarkers of allograft vasculopathy patients and non-allograft vasculopathy patients, and analyzing digital biopsy images from the transplant patient to morphologically differentiate patients which are prE allograft vasculopathy or which have active allograft vasculopathy from patients without acute allograft vasculopathy; assigning prE-, active or non-allograft vasculopathy status to a patient based on the outcome of the analysis of the clinical biomarkers and morphologic biomarkers; and where preE or active statis is assigned, treating the patient.

Abstract: The present application discloses compositions and methods for use of nucleoside modified mRNA that encode for at least one liver regenerative factor. The present invention also relates to compositions and methods for use of nucleoside modified mRNA complexed to nanoparticles. The disclosed compositions and methods are useful for treating acute liver diseases, chronic liver diseases, and/or acetaminophen (acetyl-para-aminophenol, APAP) overdose.

Abstract: A composition, including a substrate having a planar array of depressions each defined by concave walls and a moat disposed around each depression of said array of depressions.

Abstract: A method for creating an irradiation plan. The method may include receiving an irradiation therapy plan for irradiating a target with a proton beam from a gantry. The irradiation therapy plan may have a plurality of irradiation spots for delivering protons to the target. The method may include identifying a rotational profile for angular rotation of the gantry with respect to the target, a slew time for a proton beam to travel between each of the plurality of irradiation spots, and an amount of protons to be delivered to each irradiation spot. The method may also include creating an irradiation plan. The irradiation plan may include a plurality of groups of irradiation spots based on the rotational profile, the slew time, and the amount of protons to be delivered to each irradiation spot. Each group of irradiation spots may be associated with a respective portion of the angular rotation.

Abstract: Compositions for the prevention and treatment of genital herpes, comprising nucleoside modified mRNAs that encode herpes simplex virus (HSV) glycoproteins, including those involved in virus entry and immune evasion, and methods of use thereof.

Abstract: A microfluidic device contains a first layer having a plurality of channels, a second layer having a plurality of droplet makers, and a third layer having a plurality of through-holes connecting the plurality of channels to the plurality of droplet makers. The channels have a height of at least 4 times greater than the height of the droplet makers. The microfluidic device has at least 500 droplet makers in an area less than 10 cm2. The channels are formed by direct laser-micromachining and the droplet makers are formed by soft lithography molding.

Abstract: The present invention provides compositions and methods for treating cancer in a human. The invention includes administering a T cell, genetically modified to express a chimeric antigen receptor (CAR), a bispecific antibody, or a combination thereof to a subject. The CAR and bispecific antibody of the invention can comprise a human antibody, a humanized antibody, or antigen-binding fragments thereof.

Abstract: Methods and compositions are provided for treatment of peroxisomal biogenesis disorders (PBDs). More particularly, recombinant adeno-associated viruses (rAAV) provided in the form of compositions are used to deliver a nucleic acid encoding human PEX1 to host cells. The rAAVs comprise a AAV capsid, and packaged therein a vector genome comprising an AAV 5? inverted terminal repeat (ITR) sequence; a promoter; a coding sequence encoding a human PEX1; and an AAV 3? ITR.

Abstract: This disclosure demonstrates a new method to produce three dimensional multiphasic structures, including bijels, via vapor-induced phase separation (VIPS). In VIPS, the evaporation of the co-solvent from a ternary mixture of oil, water and ethanol, induces phase separation. Particles present in the mixture attach to the interface and arrest the phase separation between water and oil. VIPS enables, inter alia, the fabrication of films and coatings via spreading or spraying particle-laden suspension onto a surface without the need for an outer aqueous phase.

Abstract: The present invention includes compositions and methods for treating heart disease and/or heart failure. In one embodiment, the treatment includes administering to the subject a cell genetically modified to express a chimeric antigen receptor (CAR), comprising an antigen binding domain specific for fibroblast activation protein (FAP). In another embodiment, the treatment includes administering a cell genetically modified to express a T cell receptor (TCR) specific for an activated fibroblast.

Abstract: A super-resolution digital tomosynthesis system for imaging an object including a source configured to emit penetrating particles toward an object; a detector configured to acquire a series of projection images of the object in response to the penetrating particles from the source; positioning apparatus configured to position the source and the detector; and an imaging system coupled to the source, the detector, and the positioning apparatus. The imaging system is configured to control the positioning apparatus to position the source in relation to the detector along a scan path and to change a distance between the source and the detector, control the source and the detector to acquire the series of projection images along the scan path with the distance change between the source and detector, and construct a tomographic volume exhibiting super-resolution from data representing the acquired series of projection images.

Abstract: A small-gap device system, preferably including two or more electrodes and one or more spacers maintaining a gap between two or more of the electrodes. A spacer for a small-gap device system, preferably including a plurality of legs defining a mesh structure. A method of spacer and/or small-gap device fabrication, preferably including: defining lateral features, depositing spacer material, selectively removing spacer material, separating the spacer from a fabrication substrate, and/or assembling the small-gap device.

Abstract: A magnetic separation filter has an unsupported magnetically soft material layer having a plurality of pores, and, optionally, a passivation layer disposed on the magnetically soft material layer. The magnetic separation filter may be part of a microfluidic device having a lateral flow channel and a vertical flow magnetic separation filter. The magnetic separation device may be used to separate magnetically tagged particles, such as cells.

Abstract: A small-gap device system, preferably including two or more electrodes and one or more spacers maintaining a gap between two or more of the electrodes. A spacer for a small-gap device system, preferably including a plurality of legs defining a mesh structure. A method of spacer and/or small-gap device fabrication, preferably including: defining lateral features, depositing spacer material, selectively removing spacer material, separating the spacer from a fabrication substrate, and/or assembling the small-gap device.

Abstract: A two-step chromatography purification scheme is described which selectively captures and isolates the genome-containing rAAV vector particles from the clarified, concentrated supernatant of a rAAV production cell culture. The process utilizes an affinity capture method performed at a high salt concentration followed by an anion exchange resin method performed at high pH to provide rAAV vector particles which are substantially free of rAAV intermediates.

Abstract: Materials and methods for enhancing the effectiveness of proton radiation therapy (e.g., high linear energy transfer (LET) proton radiation therapy) against tumor cells are provided herein.

Abstract: Compositions and regimens useful in treating hemophilia A are provided. The compositions include recombinant adeno-associated virus (rAAV) with a transthyretin enhancer and promoter driving expression of a human Factor VIII.

Abstract: The present invention concerns the use of compounds and compositions for the treatment or prevention of Flavivirus infections, such as dengue virus infections and Zika virus infections. Aspects of the invention include methods for treating or preventing Flavivirus virus infection, such as dengue virus and Zika virus infection, by administering a compound or composition of the invention, to a subject in need thereof; methods for inhibiting Flavivirus infections, such as dengue virus and Zika virus infections, in a cell in vitro or in vivo; pharmaceutical compositions; packaged dosage formulations; and kits useful for treating or preventing Flavivirus infections, such as dengue virus and Zika virus infections.