The invention provides isolated achromosomal dynamic active systems (ADAS), including ADAS comprising secretion systems. These ADAS provided by the invention can be obtained by a variety of means. Various associated methods of making and using these ADAS are provided.

The invention provides isolated achromosomal dynamic active systems (ADAS), including ADAS comprising secretion systems. These ADAS provided by the invention can be obtained by a variety of means. Various associated methods of making and using these ADAS are provided.

Bile salts are steroid acids derived from cholesterol in the liver, are released into the gastrointestinal tract to aid in digestion and are thoroughly modified by the resident gut microbiota. Bile acids act as versatile signaling molecules with a variety of endocrine functions and are linked to several diseases. In particular, serum and urinary bile salts represent biomarkers for early diagnostics of liver dysfunction, yet their current detection methods are impractical and hard to scale. Here the inventors engineered engineered synthetic bile salt receptors using TcpP as sensing domains connected to E. coli CadC system which activates transcription upon dimerization. The performance of the system was assayed for various selection of promoters and they can show that fine tunable response that may be reached by changing expression levels of the bile salt receptor. By performing multiple rounds of directed evolution of the TcpP sensor the inventors obtained a collection of variants with a lower limit of detection and a higher sensitivity. Finally, they show that their bactosensor can detect pathological bile-salt concentrations in samples from patients with liver dysfunction. The present invention thus relates to bile salts bactosensor and use thereof for diagnostic and therapeutic purposes.

Bile salts are steroid acids derived from cholesterol in the liver, are released into the gastrointestinal tract to aid in digestion and are thoroughly modified by the resident gut microbiota. Bile acids act as versatile signaling molecules with a variety of endocrine functions and are linked to several diseases. In particular, serum and urinary bile salts represent biomarkers for early diagnostics of liver dysfunction, yet their current detection methods are impractical and hard to scale. Here the inventors engineered engineered synthetic bile salt receptors using TcpP as sensing domains connected to E. coli CadC system which activates transcription upon dimerization. The performance of the system was assayed for various selection of promoters and they can show that fine tunable response that may be reached by changing expression levels of the bile salt receptor. By performing multiple rounds of directed evolution of the TcpP sensor the inventors obtained a collection of variants with a lower limit of detection and a higher sensitivity. Finally, they show that their bactosensor can detect pathological bile-salt concentrations in samples from patients with liver dysfunction. The present invention thus relates to bile salts bactosensor and use thereof for diagnostic and therapeutic purposes.

Described herein are cholix-IL-10 fusion proteins, and methods of use thereof, which can be characterized by a distinct response in an individual when administered. This distinct response can comprise changes in levels of one or more markers in the individual and/or co-localization of IL-10 in the Lamina propria of the individual. Further described herein, in some embodiments, are oral formulations of the cholix-IL-10 fusion proteins. Described herein are methods for the purification of an IL-10 delivery construct, including methods for refolding and enrichment, which can result in maintenance of a high percentage of the IL-10 delivery constructs in the biologically active dimer form. Described herein are oral formulations configured for site-specific release of a therapeutic protein in the small intestines or colon. In some cases, the therapeutic protein is in the form of a dimer, such as an IL-10 delivery construct capable of crossing the gut epithelium.

Described herein are cholix-IL-10 fusion proteins, and methods of use thereof, which can be characterized by a distinct response in an individual when administered. This distinct response can comprise changes in levels of one or more markers in the individual and/or co-localization of IL-10 in the Lamina propria of the individual. Further described herein, in some embodiments, are oral formulations of the cholix-IL-10 fusion proteins. Described herein are methods for the purification of an IL-10 delivery construct, including methods for refolding and enrichment, which can result in maintenance of a high percentage of the IL-10 delivery constructs in the biologically active dimer form. Described herein are oral formulations configured for site-specific release of a therapeutic protein in the small intestines or colon. In some cases, the therapeutic protein is in the form of a dimer, such as an IL-10 delivery construct capable of crossing the gut epithelium.

The present disclosure provides non-naturally occurring fusion molecules comprising therapeutic cargo moieties, such as IL-22 with a carrier. The disclosure also provides methods and compositions for the production, purification, refolding, formulation, and administration of fusion molecules. Methods and for using the purified molecules to treat and prevent diseases or disorders are also provided herein.

A fusion gene, a recombinant novel coronavirus high-efficiency immune DNA vaccine, a construction method and use thereof are provided. The immune DNA vaccine ZD-nCor19 provided herein uses RBD protein, residues 301-538 in the S2 subunit and residues 138-369 in the N protein of the novel coronavirus as target antigens, and has specific immune synergism molecules introduced at suitable positions, and thus can simultaneously efficiently induce humoral immunity and cellular immunity, and can avoid safety problems associated with ADE that may be generated by the full-length S protein and the full-length N protein, thereby achieving dual effects of prevention and treatment. The vaccine can be used as a safe, efficient and stable vaccine variety against novel coronavirus infection.

The present invention relates to a fusion protein, a nucleotide sequence encoding such a fusion protein, the use thereof as an adjuvant or vaccine. The fustin protein comprises a bacterial exotoxin and a single chain antibody fragment (scFv) that specifically binds to a surface marker on dendritic cells. The fusion protein is advantageously administered intranasally, orally or intrapulmonarily.

The present invention relates to a fusion protein, a nucleotide sequence encoding such a fusion protein, the use thereof as an adjuvant or vaccine. The fustin protein comprises a bacterial exotoxin and a single chain antibody fragment (scFv) that specifically binds to a surface marker on dendritic cells. The fusion protein is advantageously administered intranasally, orally or intrapulmonarily.