CGT

The efficiency of recombinant Adeno-associated virus vectors (AAV) transducing host cells is very low, limiting their therapeutic potential in patients. There are several cellular pathways interacting and interfering with the journey of the AAV from the cell surface to the nucleus, opening the possibility to enhance AAV transduction by modifying these interactions. In this study, we explored the results of AAV hepatic transduction when different mTOR inhibitors.- rapamycin, MLN0128, RapaLink-1 -were used in preconditioned juvenile and adult mice.

The paraventricular nucleus of the thalamus (PVT) controls goal-oriented behavior through its connections to the nucleus accumbens (NAc). We previously characterized Glut2aPVT neurons that are activated by hypoglycemia, and which increase sucrose seeking behavior through their glutamatergic projections to the NAc. Here, we identified glucokinase (Gck)-expressing neurons of the PVT (GckaPVT) and generated a mouse line expressing the Cre recombinase from the glucokinase locus (GckCre/+ mice).

The blood-brain barrier (BBB) protects the central nervous system (CNS) from harmful blood-borne factors. Although BBB dysfunction is a hallmark of several neurological disorders, therapies to restore BBB function are lacking. An attractive strategy is to repurpose developmental BBB regulators, such as Wnt7a, into BBB-protective agents. However, safe therapeutic use of Wnt ligands is complicated by their pleiotropic Frizzled signaling activities.

Creatine deficiency disorders are inborn errors of creatine metabolism, an energy homeostasis molecule. One of these, guanidinoacetate N-methyltransferase (GAMT) deficiency, has clinical characteristics that include features of autism, self-mutilation, intellectual disability and seizures with approximately 40% having a disorder of movement; failure to thrive can also be a component. Along with low creatine levels, guanidinoacetic acid (GAA) toxicity has been implicated in the pathophysiology of the disorder.

Here we administered Cre-dependent shRNA to knock-down _Scn8a_ (thus Nav1.6) in Cre-expressing glutamatergic neurons in preBötC and quantified mRNA per glutamatergic neuron. We used adult Vglut2Cre mice (10-14 weeks old) and injected 50 nL of AAVs carrying the shRNA. We used _in situ_ hybridization (RNAscope Fluorescent Assay) to label mRNA of _Scn8a_ and to identify transduced glutamatergic neurons in the preBötC for RNA quantification at 2 and 6 weeks after injection.

Chimeric antigen receptor (CAR) T cell therapy has yielded impressive clinical results in hematological malignancies and is a promising approach for solid tumor treatment.

Though chimeric antigen receptor (CAR) expressing T cells have proven success in hematologic malignancies, their effectiveness in solid tumors has been largely unsuccessful thus far. We found that some olfactory receptors are expressed in a variety of solid tumors of different histological subtypes, with a limited pattern of expression in normal tissues.

Persistence of chronic hepatitis B (CHB) is attributed to maintenance of the intrahepatic pool of the viral covalently closed circular DNA (cccDNA), which serves as the transcriptional template for all viral gene products required for replication. Current nucleos(t)ide therapies for CHB prevent virus production and spread but have no direct impact on cccDNA or expression of viral genes. We describe a potential curative approach using a highly specific engineered ARCUS nuclease (ARCUS-POL) targeting the hepatitis B virus (HBV) genome.

RESULTS : PR-specific expression of _PRLΔE1_ was observed in the following canine models of progressive inherited retinal degeneration (IRD): _RPGR_-XLPRA1 and _NPHP5_-LCA. In _RPGR_-XLPRA2 carrier retinas that undergo random X-inactivation, patches of_ PRLΔE1 _expression correlated with patches of PR degeneration. However, we did not observe expression of _PRLΔE1_ 24 hrs and 2 wks after light exposure that triggers acute rod loss in the canine RHO-T4R model of adRP. No _PRLΔE1 _expression was seen either in the _CNGB3_-ACHM3 retina that undergoes extremely slow cone degeneration.

Thyrotropin-releasing hormone (TRH) plays a central role in metabolic homeostasis, and single-cell sequencing has recently demonstrated that vagal sensory neurons in the nodose ganglion express thyrotropin-releasing hormone receptor 1 (TRHR1). Here, in situ hybridization validated the presence of TRHR1 in nodose ganglion (NG) neurons and immunohistochemistry showed that the receptor is expressed at the protein level. However, it has yet to be demonstrated whether TRHR1 is functionally active in NG neurons.