The present invention relates to a Lipase enzyme comprising an amino acid sequence that has at least 90% sequence identity with SEQ ID NO 1, or comprising a functional fragment thereof encompassing position Q55, with the proviso that the lipase enzyme has a substitution of an amino acid with a basic side chain at neutral pH in position Q55.

The present invention relates to a Lipase enzyme comprising an amino acid sequence that has at least 90% sequence identity with SEQ ID NO 1, or comprising a functional fragment thereof encompassing position Q55, with the proviso that the lipase enzyme has a substitution of an amino acid with a basic side chain at neutral pH in position Q55.

The invention provides highly effective and versatile CRISPR/Cas protein variants, compositions, methods and uses thereof in gene editing. More specifically, the invention relates to PAM-reduced or PAM-abolished Cas proteins and chimeras, complexes and conjugates thereof, genetic editing systems and to therapeutic and non-therapeutic methods and uses of the PAM-reduced or PAM-abolished Cas proteins.

Provided herein are compositions and methods for treating, reducing, preventing, inhibiting, mitigating, ameliorating, or slowing ocular replication or infections, such as viral conjunctivitis. Certain embodiments of the present disclosure relate to product combinations that include one or more ribonuclease, such as ranpirnase, or a variant, derivative, analogue, fragment, or pharmaceutically acceptable salt thereof, and one or more additional therapeutic agent, such as a vasoconstrictor, an antibiotic, an immunomodulatory compound, or a steroid.

Provided herein are methods and compositions for inhibiting p97, for the treatment of a motor neuron disease in a subject, or a symptom thereof. Upon treatment, the motor neuron disease, or a symptom thereof is reduced in the subject.

The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.

Disclosed are compositions and formulations of non-porcine lipase and methods of treatment and manufacture thereof.

Provided herein are gene editing systems and/or compositions comprising RNA guides targeting HAO1 for use in genetic editing of the HAO1 gene. Also provide herein are methods of using the gene editing system for introducing edits to the HAO1 gene and/or for treatment of primary hyperoxaluria (PH), and processes for characterizing the gene editing system.

A method for gene editing in a vertebrate brain comprising: intravascular administration of a brain penetrable viral vector including a target sequence in a genomic locus of interest and a CRISPR enzyme; genomic integration via Non-Homologues End Joining (NHEJ) in post-mitotic neurons; and editing a monopartite cell-type specific gene via NHEJ knock-in a sgRNA flanked by self-cleaving ribozymes into 3′UTR to use an endogenous promoter for sgRNA expression.

The present disclosure is directed to methods of treating a steatosis-associated disorder by administering a therapeutic agent selected from a lysosomal enzyme, an autophagy-inducing agent, or a combination thereof. Steatosis-associated disorders discussed herein include GSD Ia, GSD Ib, GSD Ic, NAFLD, and NASH. Other embodiments are directed to methods of reversing steatosis, modulating autophagy, inducing autophagy, and reversing glycogen storage.