An apparatus comprising a magnetic assembly and methods for operating the apparatus are provided. The magnetic assembly may be used to manipulate molecules in a liquid preparation, for example to isolate or separate the molecules from the liquid. The magnetic assembly may be used to wash and/or isolate nucleic acid molecules of interest from a liquid preparation.

Described herein are methods of generating a library of cells expressing a plurality of polypeptides or recombinant polypeptides activated by an antigen and methods of panning said library of cells against a target antigen. The methods can be utilized for screening a library of chimeric antigen receptors reactive to a target antigen.

MHC multimer expression constructs are provided that contiguously encode an MHC-binding peptide, MHC molecule chains and a multimerization domain in the construct such that expression in a host cell results in production of peptide-loaded MHC (pMHC) multimers by the host cell. The multimers can further comprise oligonucleotide barcodes. Peptide exchange can be performed with a plurality of pMHC multimers to create pMHC multimer libraries. Methods of making and using the pMHC multimers and libraries are also provided. Peptide-loaded MHC Class I and MHC Class II multimers, and libraries thereof, are provided.

Provided are a method for promoting the lipolysis and fatty acid oxidative metabolism in mammals or cells derived from mammals, a method for downregulating the fat content and the weight of a mammalian body, as well as a method for increasing the intracellular cAMP concentration, increasing the phosphorylation degree and the activity of the hormone-sensitive esterase HSL, enhancing the transcription activity of PPAR alpha and increasing the activities of enzymes involved in a fatty acid beta oxidation process. By simulating the expression of a protein corresponding to a gene responsible for the phosphorylation of the Fas-associated death domain protein, or treating and acting on mammals or cells derived from mammals with a material that can increase the phosphorylation degree of the Fas-associated death domain protein, said methods increases the phosphorylation of the Fas-associated death domain protein.

Compositions and methods for gene editing are provided. The methods employ an oligo-based annealing mechanism that is rooted in the process of DNA replication rather than homologous recombination (HR). Oligo incorporation efficiencies are comparable and often exceed those of CRISPR/cas9 editing without the need for double strand breaks (DSBs). By relying on the multiplex annealing of oligos rather than DSBs the process is highly scalable across a genomic region of interest and can generate many scarless modifications of a chromosome simultaneously. Combinatorial genomic diversity can be generated across a population of cells in a single transformation event; genomic landscapes can be traversed through successive iterations of the process, and genome-wide changes can be massively parallelized and amplified through systematic strain mating.

Compositions and methods for gene editing are provided. The methods employ an oligo-based annealing mechanism that is rooted in the process of DNA replication rather than homologous recombination (HR). Oligo incorporation efficiencies are comparable and often exceed those of CRISPR/cas9 editing without the need for double strand breaks (DSBs). By relying on the multiplex annealing of oligos rather than DSBs the process is highly scalable across a genomic region of interest and can generate many scarless modifications of a chromosome simultaneously. Combinatorial genomic diversity can be generated across a population of cells in a single transformation event; genomic landscapes can be traversed through successive iterations of the process, and genome-wide changes can be massively parallelized and amplified through systematic strain mating.

This disclosure relates to methods for identifying molecular arrangements useful in managing diseases or conditions. In certain embodiments, this disclosure relates to treating an immune regulated disease comprising administering to a subject in need thereof an effective amount of a grouped molecular arrangement comprising a specific binding agent to CD19, a specific binding agent to CD3, and IL-12. In certain embodiments, this disclosure relates to screening test compounds comprising providing a library of multifunctional binding specificities and contacting the library with cells to evaluate in vitro therapeutic potential.

The presently disclosed subject matter relates to “Randomized Configuration Targeted Integration” (also referred to herein as “Randomized Chain Targeted Integration”) (RCTI) strategies for the generation and identification of host cells capable of expressing recombinant proteins, e.g., monoclonal antibodies, as well as compositions derived from the same, e.g., bispecific antibodies, and other complex format proteins, e.g., membrane protein complexes and other difficult to express molecules.

The present invention relates to the fields of molecular medicine and targeted delivery of therapeutic or diagnostic agents to cells outside the vascular system and into the parenchymal tissue of organs within the body. More specifically, the present invention relates to the methods used to identify membrane receptors or transporters capable of carrying cargo specifically targeted to the parenchymal tissue of the brain and to in vivo enrichment methods for selecting peptides that are transported across the blood-brain barrier (“BBB”), or analogously, across other membrane containing organs or structures, such as liver, spleen, kidney and tumors.

Among other things, motility of at least one individual microorganism or a change in motility of at least one individual microorganism or both is or are characterized. The characterized motility or change in motility is used to detect the presence or count of the at least one individual microorganism, or determine the identity of a species or strain of the at least one individual microorganism, or determine a susceptibility of the at least one individual microorganism to one or more antibiotics or other antimicrobials.