The present disclosure relates to methods, formulations and devices for the delivery and therapeutic administration of polynucleotides encoding AADC. The present disclosure relates to methods, formulations and devices for the delivery and therapeutic administration of AAV vectors which include polynucleotides encoding AADC. The present disclosure relates to methods, formulations and devices for the delivery and therapeutic administration of polynucleotides encoding AADC in the treatment of neurological diseases, disorders and conditions, including Parkinson's Disease.

Provided herein are biocatalysts and systems thereof for pterin-dependent enzymes and pathways and methods of making and using the same.

The present disclosure relates to an approach, referred to as Regionally Activated Interstitial Drugs (RAID), that does not require viral vectors, but allows for tunable, noninvasive, long-term neuromodulation with small molecules. RAID utilizes noninvasive delivery of an engineered protein enzyme into the brain, which then binds to the brain parenchyma and can locally convert a blood-brain-barrier (BBB)-permeable inert prodrug into an active neuromodulatory drug. As long as the RAID enzyme is present in the parenchyma, localized neuromodulation can be achieved with systemic administration of the BBB-permeable prodrug even in the absence of the opened BBB. Alternatively, gene delivery encoding the RAID enzyme offers prolonged expression and precise spatial control, enabling long-term and adaptable neuromodulation.

The present invention provides recombinant Escherichia coli for producing glutarate, a construction method and use thereof. A double-plasmid recombinant bacterium is constructed through molecular biological means for co-expressing an aldehyde synthase (AAS) gene, an amine oxidase Mao (gene) and an aldehyde dehydrogenase (Glox) gene. The constructed expression plasmids are introduced into the Escherichia coli to reconstruct to obtain recombinant cells. A recombination strain for efficiently producing glutarate is obtained through amicillin resistance and kanamycin resistance combined plate screening. Efficient production of the glutarate is achieved by optimizing concentration of a substrate, cell concentration and a transformation temperature. L-lysine with a concentration of 30 g/L may be transformed into 19.65 g of glutarate through reactions for 30 h under transformation conditions that the cell concentration is 30 g/L, the pH value is 8 and 6 mM of NAD.sup.+ is additionally added, wherein a transformation rate may be 65.3%.

The present invention is directed to compositions and methods for treating aromatic L-amino acid decarboxylase (AADC) deficiency. This invention includes a method of treating AADC deficiency in a pediatric subject, comprising the steps of: (a) providing a pharmaceutical formulation comprising an rAAV2-hAADC vector, (b) stereotactically delivering the pharmaceutical formulation to at least one target site in the brain of the subject in a dose of an amount at least about 1.810.sup.11 vg; wherein delivering the pharmaceutical formulation to the brain is optionally by frameless stereotaxy, and optionally wherein the dose is an amount of at least about 2.410.sup.11 vg and in some embodiments wherein the pharmaceutical formulation comprises a rAAV2-hAADC vector concentration of about 5.710.sup.11 vg/mL. This invention is also directed to methods for treating aromatic L-amino acid decarboxylase (AADC) deficiency, wherein the method optionally further comprises the step of administering a therapeutically effective dose of dopamine-antagonist to the subject such as risperidone. This invention is also directed to methods for treating aromatic L-amino acid decarboxylase (AADC) deficiency, wherein the method optionally comprises providing a pharmaceutical formulation comprising an rAAV2-hAADC vector, and empty capsids.

The disclosure in some aspects, relates to nucleic acids, compositions and kits useful for gene therapy with reduced immune response to transgene products.

Recombinant microorganisms that catabolize lignin aromatics, such as -5 linked lignin aromatics, and methods of using same to catabolize the lignin aromatics.

The present invention is directed to compositions and methods for treating aromatic L-amino acid decarboxylase (AADC) deficiency. This invention includes a method of treating AADC deficiency in a pediatric subject, comprising the steps of: (a) providing a pharmaceutical formulation comprising an rAAV2-hAADC vector, (b) stereotactically delivering the pharmaceutical formulation to at least one target site in the brain of the subject in a dose of an amount at least about 1.810.sup.11 vg; wherein delivering the pharmaceutical formulation to the brain is optionally by frameless stereotaxy, and optionally wherein the dose is an amount of at least about 2.410.sup.11 vg and in some embodiments wherein the pharmaceutical formulation comprises a rAAV2-hAADC vector concentration of about 5.710.sup.11 vg/mL. This invention is also directed to methods for treating aromatic L-amino acid decarboxylase (AADC) deficiency, wherein the method optionally further comprises the step of administering a therapeutically effective dose of dopamine-antagonist to the subject such as risperidone. This invention is also directed to methods for treating aromatic L-amino acid decarboxylase (AADC) deficiency, wherein the method optionally comprises providing a pharmaceutical formulation comprising an rAAV2-hAADC vector, and empty capsids.

The present invention relates to methods for making compounds of formula (I) including violacein, violacein analogues and derivatives thereof, and to compositions, cells, and fermentation liquids comprising the compounds resulting from these methods.

Provided is a recombinant adeno-associated viral (rAAV) vector comprising one or two of (a) to (c): (a) a nucleotide sequence encoding aromatic L-amino acid decarboxylase (AADC), (b) a nucleotide sequence encoding glucocerebrosidase (GBA1); and (c) a nucleotide sequence encoding a neurotrophic factor (NTF), such as cerebral dopamine neurotrophic factor (CDNF) or glial cell derived neurotrophic factor (GDNF), for treating neurodegenerative disorders, particularly Parkinson's disease (PD), Multiple system atrophy (MSA), Gaucher's disease (GD), and other proteinopathies. Also provided herein are viral particles comprising the rAAV vector, a pharmaceutical composition comprising the viral particles, and uses thereof.