The present invention provides a therapy for treating neuropathic pain by subpial administration of small quantities of a composition for spinal segment-specific upregulation of GAD65 (glutamatedecarboxylase) gene and VGAT (vesicular GABA transporter) gene, which is effective for induction of nociceptive effects by potentiating release of vesicular GABA from infected dorsal horn neurons into the synaptic cleft.

Disclosed are santalene synthases with improved product profile and methods for improving santalene synthases. The invention further relates to santalene compositions produced by fermentation that have a greater beta-santalene content than alpha-santalene content.

Disclosed are santalene synthases with improved product profile and methods for improving santalene synthases. The invention further relates to santalene compositions produced by fermentation that have a greater beta-santalene content than alpha-santalene content.

The present invention provides engineered tyrosine ammonia-lyase (TAL) polypeptides and compositions thereof. In some embodiments, the engineered TAL polypeptides have been optimized to provide enhanced catalytic activity while reducing sensitivity to proteolysis and increasing tolerance to acidic pH levels. The invention also provides methods for utilization of the compositions comprising the engineered TAL polypeptides for therapeutic and industrial purposes.

The present invention provides engineered tyrosine ammonia-lyase (TAL) polypeptides and compositions thereof. In some embodiments, the engineered TAL polypeptides have been optimized to provide enhanced catalytic activity while reducing sensitivity to proteolysis and increasing tolerance to acidic pH levels. The invention also provides methods for utilization of the compositions comprising the engineered TAL polypeptides for therapeutic and industrial purposes.

Constructs, host cells, fungi, seeds, plants, and methods are described herein can include a Serendipita indica terpenoid synthase (SiTPS). Such constructs host cells, fungi, seeds, plants, and methods are useful, for example, for making viridiflorol. As described herein, the basidionycete Serendipita indica, a non-specific-host root endophyte fungus, possesses a functional terpenoid synthase gene (SiTPS). Heterologous expression of SiTPS in host cells showed that the produced protein efficiently utilizes the fifteen-carbon precursor farnesylpyrophosphate (FTP) to synthesize the sesquiterpene alcohol viridiflorol, shown below.

Constructs, host cells, fungi, seeds, plants, and methods are described herein can include a Serendipita indica terpenoid synthase (SiTPS). Such constructs host cells, fungi, seeds, plants, and methods are useful, for example, for making viridiflorol. As described herein, the basidionycete Serendipita indica, a non-specific-host root endophyte fungus, possesses a functional terpenoid synthase gene (SiTPS). Heterologous expression of SiTPS in host cells showed that the produced protein efficiently utilizes the fifteen-carbon precursor farnesylpyrophosphate (FTP) to synthesize the sesquiterpene alcohol viridiflorol, shown below.

The invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and/or modulation of a cell's status, function, and/or activity.

The invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and/or modulation of a cell's status, function, and/or activity.

The present disclosure provides regulatable biocircuit systems. Such systems provide modular and tunable protein expression systems in support of the discovery and development of therapeutic modalities. In particular, the present application is directed to fusion proteins comprising a fragment of human human carbonic anhydrase 2 and a chimeric antigen receptor (CAR). The activity of the destabilizing domain can be regulated by externally administered agents.