Abstract: One aspect of the present invention relates to double-stranded RNAi (dsRNA) duplex agent capable of inhibiting the expression of a target gene. The dsRNA duplex comprises one or more motifs of three identical modifications on three consecutive nucleotides in one or both strand, particularly at or near the cleavage site of the strand. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA agents suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA agents, e.g., for the treatment of various disease conditions.

Abstract: The present invention relates to a CNNM4 inhibitor for use in the treatment of an acute or a chronic liver, kidney and/or lung disease in a subject, and to pharmaceutical compositions comprising a therapeutically effective amount of a CNNM4 inhibitor and a pharmaceutically acceptable excipient or carrier. Furthermore, the invention relates to a method for diagnosing a liver disease, a kidney disease or a lung disease in a subject, and to in vitro methods for identifying a compound potentially useful for reducing an induced CNNM4-mediated disease or condition in a cell.

Abstract: The disclosure is directed at providing molecular tools and methods for transgenes integration in the genome of host cells, in particular tools and method enabling a transposition-dependent expression of the transgene, thereby facilitating identification and selection of effectively transformed hosts.

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 invention contemplates-allele-specific gene editing based on targeting a heterozygous single nucleotide polymorphism (SNP) in a protein coding sequence associated with a genetic disease. The data shown herein demonstrates that the outcome of such gene editing creates a nonesense mutation that results in a marked and selective reduction of mutant protein without affecting wild type protein expression. Expression of a single CRISPR-Cas9 nuclease in neurons generated a high frequency of mutations in the targeted HD allele that included both small insertion/deletion mutations and viral vector insertions. Thus, as disclosed herein, allele-specific targeting of InDel and insertion mutations to heterozygous coding SNPs provides a feasible approach to inactivate autosomal dominant mutations that cause genetic disease.

Abstract: Methods and compositions for producing hemoglobin and treating alpha-thalassemia are disclosed.

Abstract: The present disclosure relates to antisense oligonucleotides, which target SNCA mRNA (e.g., at an intron exon junction) in a cell, leading to reduced expression of SNCA protein. Reduction of SNCA protein expression is beneficial for the treatment of certain medical disorders, e.g., a neurological disorder.

Abstract: Provided herein are improved delivery systems for oligonucleotides. The delivery systems comprise a liposome that comprises neutral phospholipids and an oligonucleotide that contains both P-ethoxy and phosphodiester backbone linkages, and which targets a BCL2-encoding polynucleotide. Methods of treating patients having cancer with the delivery systems are also provided.

Abstract: A composition according to an embodiment of the present invention includes nucleic acid molecules which are capable of effectively inhibiting the expression level of connective tissue growth factor (CTGF) and collagen by RNA interference (RNAi), thereby preventing or treating a variety of fibroproliferative diseases due to overexpression of CTGF or collagen.

Abstract: The present inventions provide eukaryotic cells, such as mammalian cells, that comprise adeno-associated virus (AAV) polynucleotides, including AAV capsid proteins (Cap), and are capable of expressing the polypeptides encoded by the AAV polynucleotides, and thereby are capable of producing AAV, including recombinant AAV. The eukaryotic cells also may comprise adenovirus (Ad) polynucleotides. The present inventions also provide methods of expressing AAV polynucleotides, as well as Ad polynucleotides, in eukaryotic cells, such as CHO cells, HEK 293 and BHK cells. The present inventions further provides other products and methods described herein.

Abstract: Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of SCN2A RNA in a cell or subject, and in certain instances reducing the amount of SCN2A protein in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a disease or disorder associated with a voltage-gated sodium channel protein, such as, for example, a Developmental and Epileptic Encephalopathy, an intellectual disability, or an autism spectrum disorder. Such symptoms and hallmarks include, but are not limited to seizures, hypotonia, sensory integration disorders, motor development delays and dysfunctions, intellectual and cognitive dysfunctions, movement and balance dysfunctions, visual dysfunctions, delayed language and speech, gastrointestinal disorders, neurodevelopmental delays, sleep problems, and sudden unexpected death in epilepsy.

Abstract: The invention discloses for the first time pluripotent cells, including induced pluripotent stem cells, embryonic stem cells, hypo-immune pluripotent cells, cells that have been derived therefrom, and cells that have been biologically differentiated therefrom into particular tissue lineages that are ABO blood type O Rhesus Factor negative or otherwise evade rejection resulting from blood type antigen mismatch. The invention further provides universally acceptable “off-the-shelf” pluripotent cells and derivatives thereof for generating or regenerating specific tissues and organs.

Abstract: Disclosed is an expression regulatory system for cell-specific transcription (expression) of a protein of interest, for example a cell cycle inducer that reactivates proliferation in adult or neonatal cardiomyocytes or insulin-producing beta cells. The expression regulatory system comprises a first nucleic acid that encodes a microRNA recognition element that specifically binds a target cell miR, and a translation suppressor protein; and a second nucleic acid that comprises a suppressor protein interaction motif that binds the translation suppressor protein, and a gene that encodes a protein of interest. When a cell of interest is co-transfected with the first and second nucleic acids of the system, the protein of interest expressed in a cell-specific fashion.

Abstract: The present invention relates to the technical field of nucleic acids, and in particular, to a method for precisely preparing a circular RNA with an Anabaena intron self-cleaving ribozyme. By redesigning a target nucleic acid sequence of a linear RNA, selecting a site suitable for precise cleavage by the intron self-cleaving ribozyme, and removing exon sequences from the Anabaena intron self-cleaving ribozyme, precise cyclization of RNAs after in vitro transcription is achieved. The method provided by the present invention solves the problem in the prior art that linear RNAs cannot be precisely cyclized during the process of generating circular RNAs in vitro, and provides an ideal in vitro preparation method for circular RNA applications.

Abstract: Aspects of the disclosure relate to methods and compositions useful for treating retinitis pigmentosa. In some aspects, the disclosure provides compositions and methods for delivering an interfering RNA to a subject in order to reduce expression of one or both alleles of an endogenous RHO gene (for example a mutant rho allele associated with retinitis pigmentosa) in a subject. In some embodiments, a replacement RHO coding sequence that is resistant to the interfering RNA also is delivered to the subject.

Abstract: This invention relates to recombinant Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) arrays and recombinant nucleic acid constructs encoding Type I-E CASCADE complexes, plasmids, retroviruses and bacteriophage comprising the same, and methods of use thereof for screening for variant cells of an organism.

Abstract: Provided herein is a nucleic acid detection system comprising: a CRISPR system comprising an effector protein and one or more guide RNAs designed to bind to corresponding target molecules; an RNA-based masking construct; and optionally, nucleic acid amplification reagents to amplify target RNA molecules in a sample. In another aspect, the embodiments provide a polypeptide detection system comprising: a CRISPR system comprising an effector protein and one or more guide RNAs designed to bind a trigger RNA, an RNA-based masking construct; and one or more detection aptamers comprising a masked RNA polymerase promoter binding site or a masked primer binding site. In some embodiments, the system may be used to detect viruses in samples.

Abstract: The invention relates to antisense oligonucleotides that are capable of bringing about specific editing of a target nucleotide (adenosine) in a target RNA sequence in a eukaryotic cell, wherein said oligonucleotide does not, in itself, form an intramolecular hairpin or stem-loop structure, and wherein said oligonucleotide comprises a non-complementary nucleotide in a position opposite to the nucleotide to be edited in the target RNA sequence.

Abstract: A composition for expressing a polypeptide within a target organ including a delivery particle, and at least a first mRNA sequence complexed with, encapsulated by, or otherwise associated with the delivery particle. The mRNA sequence includes a coding sequence which codes for the polypeptide, at least a first untranslated region (UTR) sequence, and at least one micro-RNA (miRNA) binding site sequence, wherein the miRNA binding site sequence is located within, immediately 5? to, or immediately 3? to, the first UTR sequence. The miRNA binding site sequence is selected so as to provide for differential expression of the coding sequence between first and second cell types comprised within the target organ. Methods for making and using the composition are provided, particularly in treatment of disease, such as cancer.

Abstract: RNA editing tools for use in systems designed to measure RNA in vivo and manipulate specific cell types are disclosed herein. An RNA sensor system comprising a) a single-stranded RNA (ssRNA) sensor comprising a stop codon and a payload; optionally wherein the ssRNA sensor further comprises a normalizing gene; and b) an adenosine deaminase acting on RNA (ADAR) deaminase; wherein the sensor is capable of binding to a ssRNA target to form a double-stranded RNA (dsRNA) duplex that becomes a substrate for the ADAR deaminase; wherein the substrate comprises a mispairing within the stop codon; and wherein the mispairing is editable by the ADAR deaminase, which editing can effectively remove the stop codon so as to enable translation and expression of the payload. A method of quantifying ribonucleic acid (RNA) levels using the RNA sensor system is also disclosed.