The present invention relates to methods and compositions for the prevention or treatment of neurodegenerative diseases.

The present invention concerns in general novel fusion proteins comprising a membrane-transferring moiety and an enzymatic moiety. The present invention further concerns a method of treating disease using said fusion proteins.

This invention provides biosensors, cell models, and methods of their use for monitoring osmolarity. Biosensors can include targeting domains, sensing domains and reporting domains. Biosensors can be introduced into cells reprogrammed to represent experimental or pathologic cells of interest. Model cells expressing the biosensors can be contacted with putative bioactive agents to determine possible activities, including as detectors of which is pH changes, as TempoOsmo accomplishes.

The present invention relates to a transgenic animal in which APEX2 is specifically expressed in a mitochondrial matrix and to uses thereof. When the transgenic animal according to the present invention is used, it is possible to overcome the limitation of being susceptible to contamination with proteins derived from other organelles or other tissue cells in existing mitochondrial proteomic studies. Accordingly, mitochondrial matrix proteomic research with a high reliability is possible, tissue-specific mitochondrial matrix proteomics can easily be analyzed, and a wide range of applications are possible in basic life science research, drug development, and diagnostic research related to mitochondrial proteomics.

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 provides a tool which exhibits excellent properties in the quantification of autophagy activity. A unimolecular FRET probe of the present invention includes an acceptor consisting of a fluorescent protein to be enzymatically degraded inside a lysosome or a vacuole; and a donor having an amino acid sequence having a sequence identity of 95% or more with respect to an amino acid sequence represented by SEQ ID NO: 1.

The present invention relates to methods and means for producing nitrogenase polypeptides in the mitochondria of plant cells. The present disclosure provides plant cells that express one or more MTP-Nif fusions and/or translational NifD-NifK and NifE-NifN fusions. The present disclosure also provides nucleic acid constructs encoding these fusions as well as expression constructs for expression and targeting of the fusions to the mitochondria of plant cells. The present disclosure also provides transgenic plants comprising the plant cells of the invention and products obtained therefrom.

A TAT-FXN fusion polypeptide useful in treating subjects diagnosed with Friedrich's Ataxia, hypertrophic cardiomyopathy, or both are disclosed, as are related methods of treatment and pharmaceutical compositions.

The present invention provides, among other things, compositions and methods for treatment of Friedrich's Ataxia based on effective targeting of a therapeutic moiety to mitochondria that can substitute for natural FXN protein activity or rescue one or more phenotypes or symptoms associated with frataxin-deficiency. In some embodiments, the present invention provides a targeted therapeutic comprising a therapeutic moiety, which is a polypeptide having an N-terminus and a C-terminus, a mitochondrial targeting sequence associated with the therapeutic moiety at the N-terminus, and a mitochondrial membrane-penetrating peptide associated with the therapeutic moiety at the C-terminus, wherein the therapeutic moiety is targeted to mitochondria upon cellular entry.

Disclosed are polynucleotides, polypeptides, and gene therapy vectors relating to biologically active methylmalonyl-CoA mutase enzymes, internally tagged with an immunoaffinity and detection epitope, which has been designed and tested in mouse models of methylmalonic acidemia (MMA). The polypeptides and polynucleotides of the present invention contain a mitochondrial leader sequence fused to tag, such as an HA, 3xFLAG, or V5 tag placed in a region of the methylmalonyl-CoA mutase enzyme that maintains mitochondrial localization and function, e.g., the 5 end of a methylmalonyl-CoA mutase polynucleotide is replaced with an engineered nucleotide sequence that encodes the endogenous mitochondrial importation sequence, a mitochondrial protease cleavage site, and a tag. The polynucleotides and polypeptides of the invention are useful to treat conditions such as MMA, and to assay both activity and biodistribution after gene therapy in varied models of MMA.