Present invention is aimed at identification of new fungal luciferin biosynthesis enzymes, nucleic acids able to encode these enzymes, and proteins able to catalyze certain stages of the fungal luciferin biosynthesis. The invention also provides for application of nucleic acids for producing said enzymes in a cell or organism. Methods for in vitro or in vivo preparation of chemical compounds identical to fungal luciferins and preluciferins are also provided. Vectors comprising nucleic acid described in the present invention are also provided. In addition, the present invention provides expression cassettes comprising the nucleic acid of the present invention and regulatory elements necessary for nucleic acid expression in a selected host cell. Besides, cells, stable cell lines, transgenic organisms (e.g. plants, animals, fungi, or microorganisms) including nucleic acids, vectors, or expression cassettes of the present invention are also provided. Present invention also provides combinations of nucleic acids to obtain autonomously luminous cells, cell lines, or transgenic organisms. In preferred embodiments, cells or transgenic organisms are capable to produce fungal luciferin from precursors. In some embodiments, cells or transgenic organisms are capable to produce fungal preluciferin from precursors. In some embodiments, cells or transgenic organisms are capable of bioluminescence in the presence of a fungal luciferin precursor. In some embodiments, cells or transgenic organisms are capable of autonomous bioluminescence. Combinations of proteins for producing luciferin or its precursors from more simple chemical compounds are also provided. A kit containing nucleic acids, vectors, or expression cassettes of the present invention for producing luminous cells, cell lines, or transgenic organisms is also provided.

Provided herein are compositions and methods for stabilizing enzymes. Also provided are systems, compositions and methods for using the stabilized enzymes to produce a desired compound.

Compounds are provided having the following structure:

##STR00001##

or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R.sup.1, R.sup.2, R.sup.3, L.sup.1, L.sup.2, G.sup.1, G.sup.2 and G.sup.3 are as defined herein. Use of the compounds as a component of lipid nanoparticle formulations for delivery of a therapeutic agent, compositions comprising the compounds and methods for their use and preparation are also provided.

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.

An apparatus includes a housing and an actuator. The housing, which defines a reagent volume that can receive a reagent container, can be removably coupled to a reaction chamber. A delivery portion of the housing defines a delivery path between the reagent volume and the reaction chamber when the housing is coupled to the reaction chamber. The delivery path includes a protrusion such that the delivery path has a discontinuous inner surface. The actuator can be moved to convey a reagent from the reagent container into the reaction chamber via the delivery path.

Synthetic adenoviruses with liver detargeting mutations and expressing an adenovirus type 34 (Ad34) fiber protein, or a chimeric fiber protein with an Ad34 knob domain, are described. The synthetic adenoviruses traffic to sites of tumors. Use of the synthetic adenoviruses for delivering diagnostic or therapeutic transgenes to tumors are also described.

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

Efficient sequence specific gene silencing is possible through the use of siRNA technology. Be selecting particular siRNAs by rational design, one can maximize the generation of an effective gene silencing reagent, as well as methods for silencing genes. Methods compositions, and kits generated through rational design of siRNAs are disclosed, including those directed to the nucleotide sequences for F12.

Synthetic adenoviruses with tropism to bone tissue are described. The synthetic adenoviruses include an adenovirus type 11 (Ad11) fiber protein or a chimeric adenovirus fiber protein having an Ad11 knob domain. The synthetic adenoviruses can also include a transgene, such as a reporter gene or a transgene encoding a factor that promotes bone regeneration or repair. Use of the synthetic adenoviruses to target bone tissue and/or to promote bone repair or regeneration is also described.

Provided herein are inhibitor-resistant luciferase mutants, and methods of use thereof. In particular, luciferase mutants are provided that are thermal stable and exhibit improved stability in the presence of luciferin break-down products, such as dehydroluciferin. Further provided are assay systems comprising inhibitor-resistant luciferase mutants and amino acid sequences of the inhibitor-resistant luciferase mutants.