The present invention relates to the engineering an animal model, preferably mammalian models, more preferably a rat model representing Charcot-Marie-Tooth disease 2A (CMT2A) harboring the p.Arg364Trp or p.His361Tyr Mfn2 mutation, whose human counterpart results in a severe, early-onset axonal neuropathy. A model having the p.Arg364Trp Mfn2 mutation is based on a mutation made using zinc finger endonuclease technology in fertilized rat eggs. Cohorts of mutants and wild type littermates were characterized behaviorally and shown to develop multiple motor deficits that worsened over time. Separate cohorts of mutant and wild type rats sacrificed at 7, 40, and 48 weeks and analyzed by light microscopy showed a 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. These findings were not present in the 7-week-old cohort of Mfn2 mutants, or in wild type rats at 7 or 40 weeks. A model having the p.His361Tyr Mfn2 mutation is based on a mutation made using CRISPR/Cas9 gene editing technology. This mutation showed abnormalities in gait dynamics at 8 weeks and a lengthening of the gait cycle at 16 weeks. A genetically authentic animal model for CMT2A developing a progressive axonal neuropathy is a valuable tool for examining the pathogenesis and treatment of CMT2A.

Application for MDR TNBC significantly increasing the efficacy of TNBC treatment and address a global health concern by blocking the ability of mitochondria to fuse together and with other organelles through a nanomedicine therapy. The development of a dual targeted nanomedicine therapy targeting the epidermal growth factor receptor on the surface of TNBC cancers cells and subcellular targeting of mitochondria through mitofusin 2 (MFN2) targeting (mitofusin mediates inter-mitochondrial fusion and fusion of mitochondria with the endoplasmic reticulum). The combination therapy delivers an MFN2-peptidepolymer construct for blocking MFN2 along with a low dose of BAM? (a BAX activator). Transient blocking of MFN2 reduces cellular energy capacity (through decreased mitochondrial fusion), decrease total protein production (by decreased mitochondrial coupling to the endoplasmic reticulum), increases the susceptibility of the cell to paclitaxel or BAM? (increased efficacy of lower dose), with minimal toxicity to normal cells (as IVIFN2 blocking inhibits mitochondrial fusion not mitochondrial function).

Compositions of modulators of acyl-CoA lysocardiolipin acyltransferase 1 (ALCAT1) expression, function or activity are provided. In particular, inhibitors of ALCAT1 are useful in treating metabolic diseases, cardiac diseases and, in general diseases associated with mitochondrial dysfunction. Assays for identification of novel ALCAT1 modulators are provided.

The present invention relates to the engineering an animal model, preferably mammalian models, more preferably a rat model representing Charcot-Marie-Tooth disease 2A (CMT2A) harboring the p.Arg364Trp or p.His361Tyr Mfn2 mutation, whose human counterpart results in a severe, early-onset axonal neuropathy. A model having the p.Arg364Trp Mfn2 mutation is based on a mutation made using zinc finger endonuclease technology in fertilized rat eggs. Cohorts of mutants and wild type littermates were characterized behaviorally and shown to develop multiple motor deficits that worsened over time. Separate cohorts of mutant and wild type rats sacrificed at 7, 40, and 48 weeks and analyzed by light microscopy showed a 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. These findings were not present in the 7-week-old cohort of Mfn2 mutants, or in wild type rats at 7 or 40 weeks. A model having the p.His361Tyr Mfn2 mutation is based on a mutation made using CRISPR/Cas9 gene editing technology. This mutation showed abnormalities in gait dynamics at 8 weeks and a lengthening of the gait cycle at 16 weeks. A genetically authentic animal model for CMT2A developing a progressive axonal neuropathy is a valuable tool for examining the pathogenesis and treatment of CMT2A.

There is disclosed a peptide suitable for eliciting an immune response. The peptide corresponds to a fragment of the RAS protein, and comprises a region of 8 amino acids which includes a mutated position of the RAS protein. Said region has at least 6 amino acid residues, other than the mutated position, which are identical to the corresponding region of the RAS protein. The peptide has a point mutation at the amino acid corresponding to the mutated position, and the mutated position is position 146 or 117 of the RAS protein.

The present invention relates to a composition comprising a repressor of mitofusin gene expression, an inhibitor of mitofusin protein activity, or a mixture thereof as an active ingredient for promoting reprogramming a differentiated cell into a pluripotent stem cell, and a use thereof. The composition according to the present invention increases the efficiency of reprogramming as well as reduces the time required for reprogramming to produce pluripotent stem cells. Therefore, the present composition can be beneficially used to develop the production technology of high efficiency pluripotent stem cell and secure a large-scale culture system. Further, the present composition can be beneficially used to maintain pluripotent stem cells and screen the compounds capable of promoting the reprogramming into pluripotent stem cells.

Described herein are methods of preventing, arresting progression of or ameliorating vision loss and other conditions associated with retinitis pigmentosa and x-linked retinitis pigmentosa in a subject. The methods include administering to the subject an effective concentration of a composition comprising a recombinant adeno-associated virus (AAV) carrying a nucleic acid sequence encoding a normal retinitis pigmentosa GTPase regulator (RPGR gene), or fragment thereof, under the control of regulatory sequences which express the product of the gene in the photoreceptor cells of the subject, and a pharmaceutically acceptable carrier.

The present invention relates generally to the field of prophylaxis and therapy of metastatic cancer. In particular there is provided a protein; Ras Homology gene family, member C (RhoC) or peptide fragments thereof that are capable of eliciting anti-cancer immune responses. Specifically, the invention relates to use of RhoC or peptides derived thereof or RhoC specific T-cells for treatment of metastatic cancer. Hence, the invention in one aspect relates to RhoC specific T-cells adoptively transferred or induced in vivo by vaccination as a treatment of cancer.

Also the use of RhoC and immunogenic peptide fragments hereof in cancer treatment, diagnosis and prognosis is provided.

Aspects of the present invention include compositions and methods for discovering novel compositions and applying said compositions in treating medical conditions including aging, degenerative disease, and cancer through the modulation of molecular pathways regulating regeneration and senolysis by means of altering the embryonic-fetal and prenatal/postnatal transitional states of mammalian cells.

Technology described herein relates to a fusion protein comprising a zinc-finger domain (ZNF) of Regulating Synaptic Membrane Exocytosis Protein (RIMS); and a Ca.sub.V? Ca2+ channel subunit. Compositions comprising the fusion protein and method of treatment utilizing the fusion protein are also provided herein.