The invention relates to PD-1 binding agents that block the interaction of PD-1 with its ligands, and the use of such binding agents in the treatment, prevention and detection of disease.

A nerve in a mammal is optogenetically transduced, wherein the nerve is susceptible to stimulus by selective application of transdermal light, and a light source is applied to dermis of the mammal at or proximate to the optogenetically transduced nerve, to thereby stimulate the nerve. A wearable device for optogenetic motor control and sensation restoration of a mammal includes a wearable support, a power source at the wearable support, a controller at the wearable support and in electrical communication with a power source, and a transdermal light source coupled to the controller.

This invention relates to polynucleotides comprising a nucleotide sequence encoding a PPT1 polypeptide or a fragment thereof, vectors (viral or non-viral vectors) comprising the same, and methods of using the same for delivery of the open reading frame to a cell or a subject and to treat infantile neuronal lipofuscinosis (infantile Batten disease). The polynucleotides comprise an optimized CLN1 open reading frame.

The present disclosure relates to the genetically modified non-human animals that express a human or chimeric OX40, and methods of use thereof.

This disclosure relates to genetically modified rodent animals and rodent models of human diseases. More specifically, this disclosure relates to genetically modified rodents whose genome comprises a humanized Il1rl2 gene (coding for the IL1rl2 subunit of the IL-36R protein) and human IL-36α, β and γ ligand genes. The genetically modified rodents disclosed herein display enhanced skin and intestinal inflammation as a preclinical model of psoriasis and IBD, respectively, and serve as a rodent model of human DITRA disease.

The disclosure relates to therapeutic proteins and pharmaceutical compositions comprising said proteins, which have utility in treating various human diseases. In particular aspects, the disclosed therapeutic proteins are useful for treating human gastrointestinal inflammatory diseases and gastrointestinal conditions associated with decreased epithelial cell barrier function or integrity. Further, the disclosed therapeutic proteins are useful for treating human inflammatory bowel disease, including inter alia, Crohn's disease and ulcerative colitis.

A method of treating an injury in an organ or tissue includes administering to a subject in need thereof an agent that modulates expression and/or activity of one or more genes involved in the regeneration and functional compensation of the tissue or organ in response to the injury.

This present disclosure provides adeno-associated viral vectors, recombinant adeno-associated vims (rAAV), and methods of their use in gene therapy for treating CDKL5 deficiency disorder (CDD). Also provided are pharmaceutical compositions comprising an rAAV of the invention and a pharmaceutically acceptable carrier or excipient. These pharmaceutical compositions may be useful in gene therapy for the treatment of CDD caused by mutations in CDKL.

This disclosure relates to genetically modified immunodeficient animals which express a human or chimeric (e.g., humanized) SIRPα and/or human or chimeric (e.g., humanized) CD47, and methods of use thereof.

Fragile X syndrome (FXS) is the most common inherited form of human intellectual disability. FXS is caused by loss of function of the FMR1 gene which results in significant behavioral deficits in spatial learning and memory tests. FMR1−/− knockout mice share many of the learning deficits and decreased synaptic function encountered in FXS patients. Anecdotal evidence indicates a reduction in the amount of Reelin, a large extracellular signaling protein important for normal hippocampal synaptic plasticity, may play role in the etiology of FXS. Disclosed herein is a rAAV9 Reelin viral vector expressing a REELIN repeat R3+R6 fusion protein that is shown to rescue cognitive deficits in FMR1−/− mice as evaluated in the Hidden Platform Water Maze, Open Field and Fear Conditioning. Reelin gene therapy is therefore potentially a novel therapeutic for the treatment of Fragile X Syndrome.