Abstract: The present disclosure relates to RNAi agents able to inhibit Complement Factor B (CFB) gene expression. Also disclosed are pharmaceutical compositions that include CFB RNAi agents and methods of use thereof. The CFB RNAi agents disclosed herein may be conjugated to targeting ligands, including ligands that comprise N-acetyl-galactosanine, to facilitate the in vivo delivery to hepatocyte cells.

Abstract: A stable transformant, in which a gene of interest is incorporated into the genome, is simply and efficiently produced. A method for producing a transformant, comprising a step of introducing into a host, linear genome-introduced nucleic acid fragment(s) comprising a gene of interest and a helper plasmid for transformation having a pair of homologous recombination sequences for incorporation of the linear genome-introduced nucleic acid fragment(s), and then selecting a transformant, in which the gene of interest is incorporated into the predetermined position in the host genome and the gene of interest is expressed therein.

Abstract: The current invention provides splice-switching compounds with improved characteristics that enhance clinical applicability preferably for treating, ameliorating, preventing, and/or delaying neuromuscular disorders, more specifically DMD.

Abstract: The present disclosure relates generally to compositions and methods for improving T cell therapy. In particular, the disclosure provides polypeptides and recombinant nucleic acid constructs and/or recombinant nucleic acids encoding polypeptides having mutations capable of altering T cell signaling, cytokine production, and/or in vivo persistence in tumors of therapeutic T cells comprising the mutation. The T cell signaling can be by NFAT, NF-?B and/or AP-1 pathways. The disclosure also provides vectors and cells including the polypeptides and/or recombinant nucleic acid constructs and/or recombinant nucleic acids of the disclosure as well as methods of preparing a T cell for use in cell therapy, and methods of identifying a mutation useful for improving T cell therapy.

Abstract: Provided herein are materials and methods for in situ labeling of a biological sample for use in spatial analysis of one or more analytes in the biological sample. In some aspects, in situ labeling of a biological sample includes labeling the biological sample with one or more spatial barcodes.

Abstract: The present disclosure relates generally to novel lipid nanoparticle (LNP)-based compositions useful for, e.g., the delivery of a site-specific endonuclease or a nucleic acid molecule encoding same, into a target cell. Some embodiments of the disclosure relate to compositions and methods for editing the genome of a cell, which involve contacting the cell with an LNP composition as described herein.

Abstract: Provided is a pharmaceutical composition for the treatment of a disease associated with upregulated periostin expression or periostin splice variant switching, which pharmaceutical composition comprises, as an active ingredient, a nucleic acid capable of inducing skipping of exon 17 in periostin gene transcription and/or a nucleic acid capable of inducing skipping of exon 21 in periostin gene transcription. The pharmaceutical composition of the present invention can treat a disease associated with upregulated periostin expression or periostin splice variant switching, while preventing complete inhibition of the functions of periostin.

Abstract: DNA cleaving enzymes are disclosed. The DNA cleaving enzymes are fused to a heterologous DNA binding domain that is designed to bind to a target nucleic acid sequence. Nucleic acids and expression cassettes encoding the DNA cleaving enzymes are also provided. Methods for genome editing using the DNA cleaving enzymes, fusion proteins, and compositions thereof are disclosed herein.

Abstract: Disclosed is a composition for preventing or treating a degenerative brain disease. The composition includes, as an active ingredient, a MECP2 inhibitor for treating the degenerative brain disease, a polynucleotide encoding the MECP2 inhibitor or a recombinant virus containing the MECP2 inhibitor. The composition is useful for the treatment of a degenerative brain disease (particularly Alzheimer's syndrome) caused by beta-amyloid. In addition, the composition is effective in improving or ameliorating deterioration of cognitive functions and social deficits caused by Alzheimer's syndrome.

Abstract: The present invention refers to an in vitro method for predicting cardiotoxicity risk in a cancer patient receiving, or susceptible to receive, anthracyclines chemotherapy based on the determination of the expression levels of a combination of 10 circulating miRNAs consisting of miRNA 16-5p, miRNA 22-3p, miRNA 30b-5p/30c-5p, miRNA 92b-3p, miRNA 148a-3p, miRNA-150-5p, miRNA-192-5p, miRNA 215-5p, miRNA 486-3p/486-5p and miRNA-4732-3p, in a biological sample isolated from the patient. The present invention also refers to said set of 10 circulating miRNAs for its use as biomarker of prediction of cardiotoxicity risk in cancer patients receiving, or susceptible to receive, anthracyclines chemotherapy. Finally, a method for the prevention of cardiotoxicity, in patients receiving or susceptible to receive anthracyclines chemotherapy, that comprises modulating the expression levels of the set of said 10 circulating miRNAS is contemplated.

Abstract: The present disclosure provides methods of treating a subject having a liver disease or type 2 diabetes, and methods of identifying subjects having an increased risk of developing a liver disease or type 2 diabetes.

Abstract: Provided herein are methods and compositions for increasing fetal hemoglobin levels in a cell by disrupting BCL11A expression at the genomic level. Also provided herein are methods and compositions relating to the treatment of hemoglobinopathies by reinduction of fetal hemoglobin levels.

Abstract: The present disclosure discloses a Bacillus subtilis efficiently-induced expression system based on an artificial series promoter, and belongs to the technical field of gene engineering. According to the present disclosure, an efficient artificial series constitutive promoter is used, and by compositely designing the promoter and elements (a repressor and a binding site thereof) relevant to an operon, the activity of the constitutive promoter is regulated and controlled by an inducer to finally construct the B. subtilis efficiently-induced expression system induced by the inducer. The result indicates that compared with a P43 strongly constitutive promoter, the activity of the artificial series promoter in the system is about 15 times higher. The activity of the promoter can be accurately controlled by adding different concentrations of inducers.

Abstract: The present disclosure describes compositions of matter comprising a ribonucleoprotein complex comprising a nucleic acid-guided nuclease and a guide RNA, and further comprising a blocking nucleic acid molecule represented by Formula IV, wherein Formula IV in the 5?-to-3? direction comprises: T-D-M-A-Lp-C; wherein T is 17-31 nucleotides in length; D is 0-15 nucleotides in length; M is 1-25 nucleotides in length; A is 0-15 nucleotides in length and comprises a sequence complementary to D; and L is 3-25 nucleotides in length; p is 0 or 1; C is 4-15 nucleotides in length and comprises a sequence complementary to T; and wherein the blocking nucleic acid molecule comprises a sequence complementary to a gRNA.

Abstract: Compositions, methods and kits are disclosed for high-sensitivity single molecule digital counting by the stochastic labeling of a collection of identical molecules by attachment of a diverse set of labels. Each copy of a molecule randomly chooses from a non-depleting reservoir of diverse labels. Detection may be by a variety of methods including hybridization based or sequencing. Molecules that would otherwise be identical in information content can be labeled to create a separately detectable product that is unique or approximately unique in a collection. This stochastic transformation relaxes the problem of counting molecules from one of locating and identifying identical molecules to a series of binary digital questions detecting whether preprogrammed labels are present. The methods may be used, for example, to estimate the number of separate molecules of a given type or types within a sample.