The present invention provides a novel fusion polypeptide containing a catalytic domain of NPP1 fused to a targeting moiety, nucleic acids encoding the fusion polypeptide, a vector containing the nucleic acid integrated thereinto, a host cell transformed with the vector and pharmaceutical compositions comprising the fusion polypeptide.

The present disclosure relates to compounds for activating the enzymatic activity of an E3 ubiquitin ligase and methods for treating a disease or disorder in a subject with diminished E3 ubiquitin ligase enzymatic activity. In some embodiments, the present disclosure provides a compound of Formula I

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or a compound of Formula II.

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or pharmaceutically acceptable salts thereof.

The present invention relates to a method of ligating a first peptide via its C-terminus to the N-terminus of a second peptide, wherein the reaction is catalyzed by an asparagine/aspartate (Asx) peptide ligase OaAEPI Cys247Ala having the amino acid sequence of SEQ ID NO: 1. Further encompassed are a method of preparing a dimer, oligomer, or multimer of one or more peptides of interest and a method of modifying or tagging the surface of a target cell by one or more peptides of interest. Also encompassed in the invention are the ligated peptides and/or tagged target cells obtainable according to any of the methods, the peptide ligase OaAEPI Cys247Ala having the amino acid sequence of SEQ ID NO: 1, as well as kits comprising said peptide ligase.

The present invention relates to the field of ligases. More specifically it relates to novel and highly efficient ATP-dependent DNA ligases with a unique ligase activity making the ligase particularly useful in a variety of molecular biology techniques. Furthermore, the invention relates to compositions and kits comprising the DNA ligase, methods for its manufacture and use.

Disclosed herein is iCP-mParkin. The iCP-mParkin exhibits biological features suitable for treating neuronal cell damage-related diseases. Thus, the iCP-mParkin provided herein can be used in a composition or method for treating, preventing, or alleviating Parkinson's disease, Alzheimer's disease, and Huntington's disease. Furthermore, the iCP-mParkin is higher in stability than conventional iCP-Parkin and as such, is suitable for use as a protein medicine. In addition, the iCP-mParkin obtained by the preparation method provided herein is of high purity and the preparation method is suitable for mass production.

This present disclosure provides recombinant adeno-associated virus (rAAV) and methods of their use in gene therapy for treating propionic acidemia (PA). Also provided are pharmaceutical compositions comprising a rAAV of the invention and a pharmaceutically acceptable carrier or excipient. These pharmaceutical compositions may be useful in gene therapy for the treatment of PA caused by a mutation in propionyl-CoA carboxylase α-subunit (PCCA) or a mutation in propionyl-CoA carboxylase β-subunit (PCCB).

Methods and compositions for modulating a target genome are disclosed.

The present invention concerns a novel method for the modification and/or custom-made design of artificial non-ribosomal peptide synthetases (NRPSs) from naturally available NRPSs. The artificial NRPSs are of predetermined length and amino acid composition and sequence. Via fusion of well-defined NRPS units (so-called “exchange units”) in a certain manner, using a specific sequence motif in the linker areas it is possible to construct artificial and/or modified NRPS assembly lines, which have the ability of synthesizing peptides of a desired structure.

The present invention relates to methods and compositions for reducing the risk and severity of C. difficile infection. It is based, at least in part, on the discovery that a restricted fraction of the gut microbiota, including the bacterium Clostridium scindens, contributes substantially to resistance against C. difficile infection. Without being bound by any particular theory, it is believed that this is achieved through the biosynthesis of secondary bile acids.

The present invention provides a method for synthesizing DNA, which includes: (a) providing an oligonucleotide components library as a material for synthesizing DNA, wherein an oligonucleotide component is a short oligonucleotide chain whose new end and trailing end are OH groups; (b) analyzing sequence information of a DNA to be synthesized to obtain an oligonucleotide components combination order; (c) using the oligonucleotide components library to arrange an oligonucleotide component order according to the oligonucleotide components combination order; (d) phosphorylating the new end of a first-order oligonucleotide; (e) combining the first-order oligonucleotide with a complementary oligonucleotide of the first-order oligonucleotide to obtain a first-order double-stranded oligonucleotide; (f) combining a second-order oligonucleotide in the oligonucleotide components combination order with a complementary oligonucleotide of the second-order oligonucleotide to obtain a second-order double-stranded oligonucleotide; (g) ligating the phosphorylated new end of the first-order oligonucleotide with the trailing end of the second-order oligonucleotide to obtain a synthetic oligonucleotide having an OH group as the new end; and (h) repeating the above steps (d) to (g) to sequentially elongate the synthetic oligonucleotide until the DNA sequence to be synthesized is completed.