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.

A polynucleotide encoding a modified luciferase polypeptide. The modified luciferase polypeptide has at least 60% amino acid sequence identity to a wild-type Oplophorus luciferase and includes at least one amino acid substitution at a position corresponding to an amino acid in a wild-type Oplophorus luciferase of SEQ ID NO:1. The modified luciferase polypeptide has at least one of enhanced luminescence, enhanced signal stability, and enhanced protein stability relative to the wild-type Oplophorus luciferase.

The invention provides a method of selecting a mutant polypeptide having lysine demodification, in particular lysine deacylation, activity, wherein the method comprises the following steps (a) incubating a mutant polypeptide having an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 1 with a peptide or polypeptide comprising an inactivated essential lysine residue; and (b) determining the activity of the mutant polypeptide to activate the peptide or polypeptide comprising the inactivated essential lysine residue, wherein the mutant polypeptide and the peptide or polypeptide comprising an inactivated essential lysine residue are incubated in a biological cell. The invention furthermore relates to an acylated luciferase, particularly Firefly luciferase, and uses thereof. The present invention furthermore relates to a mutant polypeptide comprising an amino acid sequence having at least 98% sequence homology with SEQ ID NOs: 2, 3, 4, 5 or 6 and having lysine demodification, in particular lysine deacylation, activity, wherein the mutant polypeptide is not identical to SEQ ID NO: 1. The invention also relates to the mutant polypeptide of the invention and a peptide or polypeptide comprising an inactivated essential lysine residue for use in treating cancer.

The present invention relates to compositions comprising and methods of producing genetically engineered bacteriophages, bacteriophage-like particles and non-replicating transduction particles (NRTPs) that contain non-native tail fibers that display altered host specificity and/or reactivity. The present invention also relates to methods of using these bacteriophages and NRTPs for the development of novel diagnostics, therapeutics and/or research reagents for bacteria-related diseases.

The present disclosure provides a monitoring device comprising a test composition, a test element comprising a test portion to which the test composition is releasably adhered, a detection reagent, and a container comprising a first end with an opening and a second end opposite the first end. The test composition comprises a predetermined quantity of tracer analyte. The container is configured to receive the test portion and configured to be operationally coupled to an analytical instrument. The tracer analyte and the detection reagent each are capable of participating in one or more chemical reaction that results in the formation of a detectable product. A method of using the monitoring device to assess the efficacy of a washing process is also provided.

Provided herein are systems and methods for characterizing target/ligand engagement. In particular, luciferase-labeled polypeptide targets are used to detect or quantify target/ligand engagement (e.g., within a cell or cell lysate).

Described herein are block copolymers, and methods of making and utilizing such copolymers. The described block copolymers are disruptive of a cellular membrane, including an extracellular membrane, an intracellular membrane, a vesicle, an organelle, an endosome, a liposome, or a red blood cell. Preferably, in certain instances, the block copolymer disrupts the membrane and enters the intracellular environment. In specific examples, the block copolymer is endosomolytic and capable of delivering an oligonucleotide (e.g., an mRNA) to a cell. Compositions comprising a block copolymer and an oligonucleotide (e.g., an mRNA) are also disclosed.

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.

Described herein are block copolymers, and methods of making and utilizing such copolymers. The described block copolymers are disruptive of a cellular membrane, including an extracellular membrane, an intracellular membrane, a vesicle, an organelle, an endosome, a liposome, or a red blood cell. Preferably, in certain instances, the block copolymer disrupts the membrane and enters the intracellular environment. In specific examples, the block copolymer is endosomolytic and capable of delivering an oligonucleotide (e.g., an mRNA) to a cell. Compositions comprising a block copolymer and an oligonucleotide (e.g., an mRNA) are also disclosed.

A polynucleotide encoding a modified luciferase polypeptide. The modified luciferase polypeptide has at least 60% amino acid sequence identity to a wild-type Oplophorus luciferase and includes at least one amino acid substitution at a position corresponding to an amino acid in a wild-type Oplophorus luciferase of SEQ ID NO:1. The modified luciferase polypeptide has at least one of enhanced luminescence, enhanced signal stability, and enhanced protein stability relative to the wild-type Oplophorus luciferase.