The present invention relates to an enzyme-catalyzed process for producing UDP-galactose from low-cost substrates uridine monophosphate and D-galactose in a single reaction mixture. Said process can be operated (semi)continuously or in batch mode. Said process can be extended to uridine as starting material instead of uridine monophosphate. Further, said process can be adapted to produce galactosylated molecules and biomolecules including saccharides, proteins, peptides, glycoproteins or glycopeptides, particularly human milk oligosaccharides (HMO) and (monoclonal) antibodies.

Transgenic non-human animal models for cellular senescence are provided herein, as are methods and materials for making and using the transgenic non-human animal models. For example, a p21-Cre mouse model for cellular senescence is provided herein.

The present invention relates to an enzyme-catalyzed process for producing UDP-N-acetyl-α-D-glucosamine (UDP-GlcNAc) from low-cost substrates uridine monophosphate and N-acetyl-D glucosamine in a single reaction mixture with immobilized or preferably co-immobilized enzymes. Uridine may be used as starting material instead of uridine monophosphate as well. Further, said process may be adapted to produce GlcNAcylated molecules and biomolecules including saccharides, particularly human milk oligosaccharides (HMO), proteins, peptides, glycoproteins, particularly antibodies, or glycopeptides, and bioconjugates, particularly carbohydrate conjugate vaccines and antibody-drug conjugates.

Systems and methods for targeted gene modification, targeted insertion, perturbation of gene transcripts, and nucleic acid editing. Novel nucleic acid targeting systems comprise components of CRISPR systems and transposable elements.

Disclosed is a method for producing 3-fucosyllactose using a wild Corynebacterium glutamicum strain. In addition, using the Corynebacterium glutamicum strain, which is a GRAS strain, 3-fucosyllactose can be produced at a high concentration, high yield and high productivity.

Provided are a method for large-scale synthesis of a long-chain RNA and a method for site-specific modification of the long-chain RNA. The method for large-scale synthesis of a long-chain RNA comprises: designing short RNA fragments and splint DNA fragments; ligating; capping; and removing the splint DNA fragments and other steps. A large number of short RNA fragments and different splint DNA fragments are chemically synthesized, and then the different short RNA fragments are ligated by a biological method so as to form a target long-chain RNA. The product long-chain RNA has a low mutation rate, a plurality of the short RNA fragments can be assembled in a single reaction, and the long-chain RNA can be synthesized at a high throughput so as to fulfill the large-scale production of the long-chain RNA. In addition, by chemical modification of the short RNA fragments, the site-specific modification of the long-chain RNA can be realized.

Provided herein are, inter alia, methods of forming chemically reactive amino acids and methods of using same.

Disclosed herein are modified polymerase compositions exhibiting altered polymerase activity, which can be useful in a variety of biological applications. Also disclosed herein are methods of making and using such compositions. In some embodiments, the compositions exhibit altered properties that can enhance their utility in a variety of biological applications. Such altered properties, can include, for example, altered nucleotide binding affinities, altered nucleotide incorporation kinetics, altered photostability and/or altered nanoparticle tolerance, as well as a range of other properties as disclosed herein.

Some aspects of this disclosure provide compositions, methods, and kits for improving the specificity of RNA-programmable endonucleases, such as Cas9. Also provided are variants of Cas9, e.g., Cas9 dimers and fusion proteins, engineered to have improved specificity for cleaving nucleic acid targets. Also provided are compositions, methods, and kits for site-specific nucleic acid modification using Cas9 fusion proteins (e.g., nuclease-inactivated Cas9 fused to a nuclease catalytic domain or a recombinase catalytic domain). Such Cas9 variants are useful in clinical and research settings involving site-specific modification of DNA, for example, genomic modifications.

The present application provides systems, methods and compositions used for targeted gene modification, targeted insertion, perturbation of gene transcripts, nucleic acid editing. Novel nucleic acid targeting systems comprise components of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) systems and transposable elements.