Abstract: This disclosure describes compositions and methods that involve a first modular component and a second modular component. The first modular component includes a first target molecule coupled to a first dimerizing moiety. The second modular component includes a second target molecule coupled to a second dimerizing moiety. The first dimerizing moiety dimerizes with the second dimerizing moiety when the first dimerizing moiety binds a chemical induced proximity (CIP) inducer.

Abstract: Compositions and regimens useful in reducing one or more of: LDL-cholesterol, total cholesterol, and/or fasting triglycerides in a subject, and/or modifying fractional catabolic rate (FCR) of LDL apolipoprotein B (apoB) from baseline to a selected time point after rAAV administration are provided. The method involves administering to the human subject via a peripheral vein by infusion of a suspension of replication deficient recombinant adeno-associated virus (rAAV).

Abstract: The present invention relates to a polynucleotide configured for the treatment of a disease of retinal cone cells, such as achromatopsia, a nucleic acid vector comprising said polynucleotide, a pharmaceutical composition comprising said nucleic acid vector, a kit comprising said polynucleotide or said nucleic acid vector, a method of making said nucleic acid vector, and a method for treating a disease of the retinal cone cells.

Abstract: The present invention relates to targeted genome editing in eukaryotic cells or organisms. More particularly, the present invention relates to a composition for cleaving a target DNA in eukaryotic cells or organisms comprising a guide RNA specific for the target DNA and Cas protein-encoding nucleic acid or Cas protein, and use thereof.

Abstract: A method of processing a collection of nucleic acid sequences is provided including connecting an adaptor to one or more or each nucleic acid sequence in the collection to create a processed nucleic acid template library, wherein the adaptor includes a first DNA sequence encoding a PAM sequence and at least a tracr mate.

Abstract: The present invention relates to polynucleotides comprising a Factor IX nucleotide sequence, wherein the Factor IX nucleotide sequence comprises a coding sequence that encodes a Factor IX protein or fragment thereof and wherein a portion of the coding sequence is not wild type. The present invention further relates to viral particles comprising a recombinant genome comprising the polynucleotide of the invention, compositions comprising the polynucleotides or viral particles, and methods and uses of the polynucleotides, viral particles or compositions.

Abstract: The invention relates to biomarkers of the skin of children and, in particular, that of infants, having altered expression in the presence of urine. Such markers are particularly advantageous as they allow the skin's response to urine to be monitored. The inventors have developed methods for evaluating the efficacy in vitro of formulations in preventing the harmful effects of urine on a child's skin, using a skin model specifically capable of reproducing the characteristics of children's skin.

Abstract: The present invention provides modified aminoacyl-tRNA synthetases (ARSs) having increased reactivity with N-methyl amino acids compared to natural aminoacyl-tRNA synthetases. The modified aminoacyl-tRNA synthetases according to the present invention can aminoacylate tRNAs with their corresponding N-methyl-substituted amino acids such as N-methyl-phenylalanine, N-methyl-valine, N-methyl-serine, N-methyl-threonine, N-methyl-tryptophan, and N-methyl-leucine more efficiently than natural aminoacyl-tRNA synthetases. The present invention enables a more efficient production of polypeptides containing N-methyl amino acids.

Abstract: Provided herein are methods directed to multiplexed detection of the modulation of transcriptional activity using perturbation elements.

Abstract: The present invention is directed to a cellular biosensor system comprising (A) a repressor module comprising one or more genes, which in their cumulative gene action exert repressing and/or inhibitory effect(s) on (B), an output module comprising at least one gene comprising at least one output sequence generating one or more output signals (i) in the absence of repressing and/or inhibitory effect(s) of the repressor module (A) and (ii) in the presence of at least one recombinase expressed by (C), a recombinase module comprising at least one gene comprising at least one sequence encoding a site-specific recombinase that enables gene rearrangement in the output module resulting in one or more output signals in the absence of repressing and/or inhibitory effect(s) of the repressor module, wherein the repressing and/or inhibitory effects of the repressor module are controlled by one or more inputs that negatively affect the repressing and/or inhibitory effects of the repressor module (A).

Abstract: Methods and compositions for rapid development of reporter lines utilizing safe harbor sites in iPSCS, as well as other progenitor cells, pluripotent and multipotent stem cells and differentiated cells, and multiple Lox sites are provided.

Abstract: Provided herein are methods and compositions to make guide nucleic acids (gNAs), nucleic acids encoding gNAs, collections of gNAs, and nucleic acids encoding for a collection of gNAs from any source nucleic acid. Also provided herein are methods and compositions to use the resulting gNAs, nucleic acids encoding gNAs, collections of gNAs, and nucleic acids encoding for a collection of gNAs in a variety of applications.

Abstract: Disclosed is an adapted Madin-Darby canine kidney cell line capable of suspension culture in the absence of serum, and a chemically-defined medium for culture of the adapted MDCK cell line. Further disclosed are culture methods for growing the adapted MDCK cell line and methods for producing a vaccine from the adapted MDCK cell line grown in the chemically-defined medium.

Abstract: The present disclosure provides engineered Class 1 Type I CRISPR-Cas (Cascade) systems that comprise multi-protein effector complexes, nucleoprotein complexes comprising Type I CRISPR-Cas subunit proteins and nucleic acid guides, polynucleotides encoding Type I CRISPR-Cas subunit proteins, and guide polynucleotides. Also, disclosed are methods for making and using the engineered Class 1 Type I CRISPR-Cas systems of the present invention.

Abstract: Provided herein are methods and compositions for depleting targeted nucleic acid sequences from a sample, enriching for sequences of interest from a sample, and/or partitioning of sequences from a sample. The methods and compositions are applicable to biological, clinical, forensic, and environmental samples.

Abstract: Methods of modulating expression of a target nucleic acid in a cell are provided including introducing into the cell a first foreign nucleic acid encoding one or more RNAs complementary to DNA, wherein the DNA includes the target nucleic acid, introducing into the cell a second foreign nucleic acid encoding a nuclease-null Cas9 protein that binds to the DNA and is guided by the one or more RNAs, introducing into the cell a third foreign nucleic acid encoding a transcriptional regulator protein or domain, wherein the one or more RNAs, the nuclease-null Cas9 protein, and the transcriptional regulator protein or domain are expressed, wherein the one or more RNAs, the nuclease-null Cas9 protein and the transcriptional regulator protein or domain co-localize to the DNA and wherein the transcriptional regulator protein or domain regulates expression of the target nucleic acid.

Abstract: A system for continuous mutagenesis to facilitate directed evolution, the system including DNA polymerases carrying the novel K54E point mutation, and other point mutations including I709N, A759R, D424A (herein called K54E_LF Pol I) and this methods of use to produce and detect lines where mutagenesis is continuous and does not exhibit the usual decline in mutagenesis with sequential cloning.

Abstract: Provided are approaches to improving CRISPR-based DNA editing by performing the editing in cells in which pol ? (“POLQ”) enzyme and/or its function is reduced. Approaches are provided that are applicable to Cas9 nuclease and Cas9 nickase CRISPR editing. Also provided are kits that can contain a polynucleotide encoding a Cas9 and an agent for use in inhibiting POLQ, and/or or an expression vector configured for expressing a mutation template for use in CRISPR chromosome editing and an agent for use in inhibiting POLQ.

Abstract: The present disclosure relates to a method of obtaining a cell where fucosylation pathways are modified, leading to production of partially fucosylated and non-fucosylated protein products, specifically antibodies from the cell. The present disclosure employs the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology. The method of the present disclosure targets the Fut8 gene and GMD gene in a cell. Such products are used in developing therapeutics and biomarkers, and in diagnosis and prognosis of diseases.

Abstract: The invention relates to a vector comprising: a 5? nucleic acid that is homologous to a genomic sequence 5? of a stop codon of a constitutively expressed gene; an exogenous nucleic acid; a 3? nucleic acid that is homologous to a genomic sequence 3? of the stop codon of the constitutively expressed gene; a translation interruption-reinitiation signal operably linked to the 5? nucleic acid and the exogenous nucleic acid, wherein the translation interruption-reinitiation signal is capable of replacing the stop codon of the constitutively expressed gene.