Abstract: The present invention pertains to methods for obtaining captured polynucleotide fragments. Further provided are methods for obtaining rearranged captured polynucleotide fragments. The present invention also relates to methods for the identification of at least one compound, at least one protein, and/or at least one secondary metabolite having biological activity. Kits for performing the above methods, methods of treatment using the compounds as screened with the methods for identification of at least one compound having biological activity, as well as pharmaceutical compositions thereof, are also provided.

Abstract: Described herein are methods for making genetically modified cells by introducing combinations of genetic variants (designed or random) or constructs (genes or otherwise arbitrary DNA) into a population of cells, and for tracking each variant combination by sequentially building an array of barcodes at a common locus (chromosomal or plasmid), termed the barcode locus. Also described are the cells made by such methods.

Abstract: Methods of treatment, genetic screening, and disease models for heart conditions associated with RBM20 deficiency are disclosed. In particular, methods of treating heart conditions associated with RBM20 deficiency, including RBM20-dependent dilated cardiomyopathy and heart failure with compounds that upregulate expression of RBM20, such as all-trans retinoic acid are provided. Also disclosed are methods of genetic screening to detect the presence of a P633L mutation in RBM20 in order to identify individuals having a genetic predisposition to developing RBM20-dependent DCM. Induced pluripotent stem cell-derived cardiomyocytes (IPSC-CMs) produced by differentiation of IPSCs comprising at least one RBM20 allele encoding a P633L mutation and methods of using them in screening for therapeutics for treating RBM20-dependent DCM are also disclosed.

Abstract: The present disclosure relates to multiplex production and phenotyping of genetically engineered cells using RNA-guided nucleases and genomic barcoding. In particular, high-throughput multiplex genome editing is achieved utilizing a system that facilitates precise genome editing at desired target chromosomal loci by homology directed repair. Integration of guide RNA and donor DNA sequences as a genomic barcode at a separate chromosomal locus allows identification, isolation, and massively-parallel validation of individual variants from a pool of transformants. Strains can be arrayed according to their precise genetic modifications, as specified by donor DNA incorporation in heterologous or native genes.