The invention discloses oncogenic fusion proteins. The invention provides methods for treating gene-fusion based cancers.

Provided is a method for knocking in a gene of interest to a cell. The genome of the cell contains a negative selectable marker, e.g., a thymidine kinase gene flanked by a pair of recombinase recognition sites (RRS), e.g., attP. The method involves introducing into the cell a targeting construct that contains a gene of interest flanked by a second pair of RRS, e.g., attB. The targeting construct also contains in the vector backbone a negative selectable marker, e.g., thymidine kinase gene. When a recombinase recognizing the RRS is expressed, the recombination events between the two pairs of RRS result in the site-specific integration of the gene of interest in the genome of the cell. Upon selection based on the negative selectable marker, the parental cells, cells with undesired integration, e.g., random integration, or the integration of the vector backbone are removed.

A peptoid compound, a manufacturing method of a peptoid compound, an oligomer, a pharmaceutical composition, use of the pharmaceutical composition in the preparation of a medicament for detecting or diagnosing a disease related to tyrosine kinase HER2, and a kit for identifying circulating tumor cells are provided, the peptoid compound includes: a cysteine (Cys) subunit, a butanediamine (Nlys) subunit, a 3,4-methylenedioxybenzylamine (Npip) subunit, a 3-aminopropanic acid (Nce) subunit and a 1-naphthylamine (Na) subunit, and both the peptoid compound and the oligomer have a strong ability to bind to HER2 protein on surfaces of circulating tumor cells (CTCs), and a technology of diagnosing breast cancer on the basis of the peptoid compound can realize non-invasive and label-free rapid diagnosis, in addition, the methods for synthesizing the peptoid compound and the oligomer are simple, the preparation efficiency is high, and the production cost is low.

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.

Compositions comprising modified recombinant polymerizing enzymes are provided, along with nucleic acid molecules encoding the modified polymerizing enzymes. In some aspects, methods of using such polymerizing enzymes to synthesize a nucleic acid molecule or to sequence a nucleic acid template are provided.

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.

A therapeutic agent comprising Lon protease, or a variant or active fragment thereof, alpha-hemolysin, or a variant or active fragment thereof, CK1α1, or a variant or active fragment thereof, a c-MYB inhibitor and/or a CEBP-δ inhibitor, for use in therapy, with the proviso that the therapeutic agent does not comprise a bacteria or bacterial supernatant. Methods of production and use thereof.

A therapeutic agent comprising Lon protease, or a variant or active fragment thereof, alpha-hemolysin, or a variant or active fragment thereof, CK1α1, or a variant or active fragment thereof, a c-MYB inhibitor and/or a CEBP-δ inhibitor, for use in therapy, with the proviso that the therapeutic agent does not comprise a bacteria or bacterial supernatant. Methods of production and use thereof.

Provided herein are methods and compositions for creating a sequencing library comprising a target nucleic acid. Methods herein can comprise: contacting a nucleic acid sample to a first population of primers, a polymerase, dNTPs, and labeled ddNTPs; performing an extension reaction thereby creating an labeled extension product; contacting the extension product to a second population of primers to create a double stranded extension product comprising the target nucleic acid; contacting the double stranded extension product to a target specific enzyme under conditions allowing cleavage of at least a subset of the double stranded extension product thereby creating a cleaved target nucleic acid; and isolating the cleaved target nucleic acid.