Long-Term Rescue of a Lethal Inherited Disease by Adeno-Associated Virus–Mediated Gene Transfer in a Mouse Model of Molybdenum-Cofactor Deficiency

Molybdenum cofactor (MoCo) deficiency is a progressive neurological disorder that inevitably leads to early childhood death because of the lack of any effective therapy. In a mouse model of MoCo deficiency type A, the most frequent form of this autosomal recessively inherited disease, the affected animals show the biochemical characteristics of sulphite and xanthine intoxication and do not survive >2 wk after birth. We have constructed a recombinant-expression cassette for the gene MOCS1, which, via alternative splicing, facilitates the expression of the proteins MOCS1A and MOCS1B, both of which are necessary for the formation of a first intermediate, cyclic pyranopterin monophosphate (cPMP), within the biosynthetic pathway leading to active MoCo. A recombinant adeno-associated virus (AAV) vector was used to express the artificial MOCS1 minigene, in an attempt to cure the lethal MOCS1-deficient phenotype. The vector was used to transduce Mocs1-deficient mice at both 1 and 4 d after birth or, after a pretreatment with purified cPMP, at 40 d after birth. We report here that all Mocs1-deficient animals injected with a control AAV–enhanced green fluorescent protein vector died ∼8 d after birth or after withdrawal of cPMP supplementation, whereas AAV-MOCS1–transduced animals show significantly increased longevity. A single intrahepatic injection of AAV-MOCS1 resulted in fertile adult animals without any pathological phenotypes

Conductive hybrid carbon nanotube (CNT)– polythiophene coatings for innovative auditory neuron-multi-electrode array interfacing

Cochlear implants (CIs) are neuroprosthetic devices that restore hearing in deaf patients. They consist of a linear electrode array surgically inserted into the scala tympani of the cochlea. In this position the array directly stimulates the spiral ganglion neurons (SGNs), bypassing lost or nonfunctioning sensory hair cells. In order to reduce the energy needed to stimulate the SGNs, we attempted to improve the conductivity of the CI electrodes by creating conductive nanocomposites. We assessed the functional modification of CI platinum (Pt) pads by using multi-walled carbon nanotubes (MWCNTs) either alone or in combination with a conductive polythiophene phase, to obtain conductive nanocomposites (NCs). [...