The present disclosure provides methods for treating or ameliorating a myelin associated disease or a mitochondria associated disease that comprising administering to a subject in need thereof a frataxin replacement therapeutic compound, e.g., a fusion protein comprising frataxin.

The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are structural information on the Cas protein of the CRISPR-Cas system, use of this information in generating modified components of the CRISPR complex, vectors and vector systems which encode one or more components or modified components of a CRISPR complex, as well as methods for the design and use of such vectors and components. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. In particular the present invention comprehends the engineering of optimized modular CRISPR-Cas enzyme systems.

The disclosure provides systems, compositions, kits, and methods useful for the targeted site-specific modifications of RNA molecules. Generally, the systems, compositions, kits, and methods described herein comprise a polypeptide or a nucleic acid encoding the polypeptide. The polypeptide comprises a first domain comprising a catalytic domain of an RNA modifying enzyme and a second domain comprising a MID domain of an Argonaute (Ago) protein. The systems, compositions, kits, and methods can also comprise an oligonucleotide for targeting the polypeptide to a target RNA. A method for modifying a target RNA, comprises contacting the target RNA with a polypeptide or a nucleic acid encoding the polypeptide and with an oligonucleotide described herein. Some exemplary modifications of the target RNA include, but are not limited to, site-specific deamination of an adenosine, deamination of a cytidine, methylation (e.g., methylation at position 6) of an adenosine, and demethylation of m6-adenosine in the target RNA.

The present disclosure provides glycosyl hydrolases (e.g., OGA) comprising a ligand-dependent intein. The present disclosure also provides pharmaceutical compositions comprising the glycosyl hydrolases disclosed herein, as well as polynucleotides, vectors, cells, and kits. Methods of using the disclosed intein-containing glycosyl hydrolases are also provided herein, including methods of deglycosylating a target protein. Methods of treating a glycosylation-associated disease in a subject, as well as methods of sensitizing a cell to a desirable therapeutic outcome, are also provided herein.

Provided herein are modified cyclin F polypeptides and nucleic acid molecules encoding the same. In particular, provided herein are modified cyclin F polypeptides that have increased cytoplasmic targeting compared to wild-type cyclin F polypeptides, and functional, truncated modified cyclin F polypeptides, and nucleic acid molecules encoding the same. Also provided herein is the use of the modified cyclin F polypeptides and encoding nucleic acid molecules for enhancing motor neuron survival, inhibiting motor neuron degeneration and treating neurodegenerative conditions, in particular those associated with neuronal TDP-43 proteinopathy.

A CRISPR regulatory system is disclosed. More particularly, the CRISPR regulatory system is useful for effectively regulating expression of a target gene and contains a Cas12f1 fusion protein and an engineered Cas12f1 guide RNA Uses of the CRISPR regulatory system are also disclosed. A method of regulating expression of a target gene by using a CRISPR regulatory system containing a Cas12f1 fusion protein and an engineered Cas12f1 guide RNA is also disclosed.

The present invention relates to the field of anastasis, i.e., the process of reversal of apoptosis. More specifically, the present invention provides methods and compositions useful for studying anastasis. In one embodiment, a tracking construct of the present invention comprises Lyn11-NES-ERT2-DEVD-rtTA-3?FLAG-DEVD-ERT2-NES. In another embodiment, a construct comprises Lyn11-NES-DEVD-rtTA-3?FLAG. In a further embodiment, a construct comprises ERT2-DEVD-rtTA-3?FLAG-DEVD-ERT2.

The invention provides compositions and methods for the preparation, manufacture and therapeutic use of viral vectors, such as adeno-associated virus (AAV) particles having viral genomes encoding one or more antibodies or antibody fragments or antibody like polypeptides, for the prevention and/or treatment of diseases and/or disorders.

The present disclosure provides a fusion protein useful for treating a non-nuclear organelle associated disorder, such as a genetic disorder, e.g., Friedrich's Ataxia. The fusion protein may comprise a protein of interest to be delivered to a non-nuclear organelle; an organelle targeting sequence (OTS); a cell penetrating peptide (CPP); and a target enhancing sequence (TES); wherein the CPP is capable of interference with delivery of the protein of interest to the non-nuclear organelle; and wherein the TES prevents said interference by the CPP. The fusion protein may also comprise a protein of interest to be delivered to a non-nuclear organelle; a CPP and a TES. The present disclosure also provides methods for treating a non-nuclear organelle associated disorder by administering the fusion protein to a subject in need thereof.

The present invention relates to a polypeptide comprising at least one signaling domain and a potassium sensor which is capable of binding K.sup.+ and the first signaling domain is capable of generating a detectable signal upon binding of K.sup.+ to the potassium sensor. The invention also relates to a polynucleotide encoding said polypeptide and the use of the polypeptide in various applications for the detection of K.sup.+.