The disclosure describes engineered cells for the treatment of joint and bone disease. The cells are engineered to sense signals only found in diseased compartments and in turn produce therapeutic molecules that are secreted into the local environment.

The disclosure features methods for treating or ameliorating at least one symptom of a subject having or being prone to a muscle weakness disease, comprising administering to said subject a therapeutically effective amount of at least one recombinant polypeptide having alkaline phosphatase activity.

Provided herein are compositions that include at least two different nucleic acid vectors, where each of the at least two different vectors includes a coding sequence that encodes a different portion of an otoferlin protein, and the use of these compositions to treat hearing loss in a subject.

A method of treating a human having a condition or disease related to a bone defect characterized by at least one of: increased level of an alkaline phosphatase ligand, particularly PPi, PLP, or PEA; and decreased alkaline phosphatase activity, compared to a human without said condition or disease, comprising administering to the human a therapeutically effective amount of a polypeptide comprising the amino acid sequence of SEQ ID NO: 1, wherein the polypeptide is administered through at least one subcutaneous injection to the human in a frequency of fewer than three times each week.

A detoxification method includes the steps of inducing flow of patient blood through an extracorporeal device inlet and outlet in fluid connection to the circulatory system of a patient. Biological agents including lipopolysaccharide (LPS) contained within patient blood can be detoxified by passing patient blood over a biochemical reactor surface having attached or immobilized Saccharomyces boulardii alkaline phosphatase enzyme, with the biochemical reactor being contained within the extracorporeal device. An acyloxyacyl hydrolase enzyme may also be used on the biochemical reactor surface.

The present disclosure provides a method of treating seizure in a subject having aberrant alkaline phosphatase activities, comprising administering a therapeutically effective amount of at least one recombinant alkaline phosphatase to the subject.

The present invention relates to a prefunctionalized metallic nanoparticle (10) as a standardized basic building block of biofunctionalized nanoparticles (40), having a thiol-reactive metallic nanoparticle (12) that is prefunctionalized by a bifunctional molecule (20) that consists of an anchor component (22) and a short further-functionalization stub (24). Here, it is provided that the anchor component (22) comprises one or more dithiophosphate groups, and the short further-functionalization stub (24) is adapted for the attachment of a desired biofunctionalization (30) and is selected from the group consisting of i) an unmodified standardized oligonucleotide strand (26) having 2 to 18 bases for further-functionalization with biomolecules (30) having a terminal complementary strand (36) of the standardized oligonucleotide strand (26), and ii) a 2- to 18-base-long oligonucleotide strand (50; 60) that is modified with a terminal reactive group (52; 62) for biomolecules.

The disclosure features methods for treating hypophosphatasia (HPP) in a patient (e.g., an adult having HPP, such as an adult having pediatric-onset HPP, or an adolescent having HPP) exhibiting decreased pyrophosphate (PPi) or pyridoxal 5′-phosphate (PLP) concentrations in, e.g., a plasma sample, physical impairments, or decreased walking ability by administering a soluble alkaline phosphatase (sALP) to the patient.

Described herein are flash nanoprecipitation methods capable of encapsulating hydrophobic molecules, hydrophilic molecules, bioactive protein therapeutics, or other target molecules in amphiphilic copolymer nanocarriers.

The invention provides non-naturally occurring microbial organisms containing a fatty alcohol, fatty aldehyde or fatty acid pathway, wherein the microbial organisms selectively produce a fatty alcohol, fatty aldehyde or fatty acid of a specified length. Also provided are non-naturally occurring microbial organisms having a fatty alcohol, fatty aldehyde or fatty acid pathway, wherein the microbial organisms further include an acetyl-CoA pathway. In some aspects, the microbial organisms of the invention have select gene disruptions or enzyme attenuations that increase production of fatty alcohols, fatty aldehydes or fatty acids. The invention additionally provides methods of using the above microbial organisms to produce a fatty alcohol, a fatty aldehyde or a fatty acid.