Abstract: Aspects of the disclosure relate to phosphotriesterase (PTE) enzymes and PTE-related (PTER) enzymes and their use in hydrolyzing OPNAs.

Abstract: Engineered Streptococcus canis Cas9 (ScCas9) variants include an ScCas9 protein with its PID being the PID amino acid composition of Streptococcus pyogenes Cas9 (SpCas9-NG, an ScCas9 protein having a threonine-to-lysine substitution mutation at position 1227 in its amino acid sequence (Sc+), and an ScCas9 protein having a threonine-to-lysine substitution mutation at position 1227 and a substitution of residues ADKKLRKRSGKLATE [SEQ ID No. 4] in position 365-379 in the ScCas9 open reading frame (Sc++). Also included are CRISPR-associated DNA endonucleases with a PAM specificity of 5?-NG-3? or 5?-NNG-3? and a method of altering expression of a gene product by utilizing the engineered ScCas9 variants.

Abstract: The present inventors have found that by cultivating insect cells, into which the Cas3 gene has been introduced, at relatively low temperatures, it is possible to efficiently express recombinant Cas3 proteins with maintained activity, and by purifying the soluble fractions of these cells, it is possible to collect active forms of the recombinant Cas3 proteins in high purity and high yield.

Abstract: Disclosed herein are recombinant meganucleases engineered to bind and cleave a recognition sequence in the mitochondrial DNA (mtDNA) of a eukaryotic cell, such as a plant cell. The disclosure further relates to the use of such recombinant meganucleases in methods for producing genetically-modified eukaryotic cells, and to a population of genetically-modified eukaryotic cells wherein the mtDNA has been having modified or edited.

Abstract: Described herein are novel systems for targeting, editing or manipulating DNA in a cell or cell free environment, using novel type V B-GEn.1 or B-GEn.2 nucleases and variants thereof, as well as methods and kits for manipulating DNA. Further disclosed are novel and improved single guide RNAs.

Abstract: The information processing device includes: a cultivation information acquisition unit configured to acquire cultivation information of a cell; and a recommended condition setting unit configured to set a recommended condition for detaching the cell from a to be-processed vessel in which the cell is cultured, the cultivation information including information about the to-be-processed vessel, the recommended condition being a condition for detaching the cell by applying vibration to the to-be-processed vessel, the recommended condition setting unit being configured to set the recommended condition based on the cultivation information, with use of information concerning an association relationship between information about a cultivation condition and information about a detachment condition, the information about the cultivation condition including information about a culture vessel, the information about the detachment condition including information about a condition for applying vibration to the culture vess

Abstract: Compositions, methods, kits, and systems are provided in which a biological sample containing cells and/or viruses that include a nucleic acid of interest are treated with an amplification-compatible releasing composition that provides release of the nucleic acid from cells and/or viruses in the sample and also permits amplification of the released nucleic acids without an intervening separation step. Methods incorporating such compositions are also described, and provide simple and rapid release of nucleic acids from cells and viruses along with subsequent amplification steps. Collection devices incorporating such compositions and kits for collection, release, and amplification of nucleic acids utilizing such compositions are provided, as are systems for characterizing nucleic acids.

Abstract: The present disclosure relates to methods, compositions, and kits for isolating target nucleic acids below a target size from a sample comprising nucleic acid components. In some embodiments, the methods involve one or more aqueous two-phase system (ATPS) compositions, at least one solid phase medium, and at least one buffer. Some embodiments provide a kit comprising one or more ATPS compositions, at least one solid phase medium, and at least one buffer. Other embodiments provide methods for diagnosing a disease or condition using the methods described herein.

Abstract: Methods and compositions for modifying the coding sequence of endogenous genes using rare-cutting endonucleases and transposases. The methods and compositions described herein can be used to modify the coding sequence of endogenous genes.

Abstract: Methods and compositions for modifying the coding sequence of endogenous genes using rare-cutting endonucleases and transposases. The methods and compositions described herein can be used to modify the coding sequence of endogenous genes.

Abstract: Methods and compositions for modifying the coding sequence of endogenous genes using rare-cutting endonucleases and transposases. The methods and compositions described herein can be used to modify the coding sequence of endogenous genes.

Abstract: Methods and compositions for modifying the coding sequence of endogenous genes using rare-cutting endonucleases and transposases. The methods and compositions described herein can be used to modify the coding sequence of endogenous genes.

Abstract: Methods and compositions for modifying the coding sequence of endogenous genes using rare-cutting endonucleases and transposases. The methods and compositions described herein can be used to modify the coding sequence of endogenous genes.

Abstract: Methods and compositions for modifying the coding sequence of endogenous genes using rare-cutting endonucleases and transposases. The methods and compositions described herein can be used to modify the coding sequence of endogenous genes.

Abstract: Methods and compositions for modifying the coding sequence of endogenous genes using rare-cutting endonucleases and transposases. The methods and compositions described herein can be used to modify the coding sequence of endogenous genes.

Abstract: The present disclosure, at least in part, provides RNA cleavage based engineered bi-stable toggle switch utilizing the Programmable Endonucleolytic Scission-Induced Stability Tuning (PERSIST) platform. Also provided herein, are vectors encoding the engineered bi-stable toggle switch, and uses thereof.

Abstract: Methods of generating novel guide nucleic acids comprising a template-conserved target complementary region to a template and template-randomized region, novel guide nucleic acids generated by the methods, mixtures and complexes comprising the novel guide nucleic acids are disclosed.

Abstract: Method for detecting and barcoding the molecular changes occurring in two or more samples upon exposure to different stimuli. This disclosure herein sets for methods that allow a targeted transcriptome-imaging approach that records both gene-expression and spatial context within microscale assemblies at a single-cell and molecule resolution on biological samples. This disclosure herein sets for methods that allows the application to a variety of biological samples for the study of cellular processes, growth, and interactions between biological samples.

Abstract: Provided herein are methods for capturing a connected probe and/or a capture handle sequence to a capture domain of a capture probe.

Abstract: This invention features nucleic acid constructs which comprises reporter genes and a query sequence, wherein the query sequences encode or are RNA folded into a secondary structure and or RNA regulatory elements. These nucleic acid constructs can be used in massively parallel assay methods for perturbation profiling also disclosed herein. Such methods provide the ability to study the effect of chemical or genetic perturbations to modulate RNA within an intracellular context.

Abstract: The present invention discloses a method for screening for and identifying a desirable plant improving trait, said method comprises steps of: (a) obtaining genetic material from a sampling of a predefined source and (b) constructing an expression library from said genetic material. The aforementioned method further comprises steps of: (c) producing plants transformed with said expression library at a transformation efficiency of at least 0.05%-30%, representing at least 102-1010 trangenes; (d) screening for transformed plants expressing said desirable trait; and (e) identifying said transgene of said transformed plants expressing said desirable trait.

Abstract: Disclosures herein are directed to methods and compositions for the detection of and screening for mutations that convey phenotypic properties in a protein such as, for example, drug-resistance. Embodiments of the present disclosure include lentiviral-based compositions for enhanced mutagenesis and screening of genes encoding proteins of interest that confer drug resistance according to methods disclosed herein.

Abstract: This invention relates to compositions of matter, methods, modules and instruments for automated mammalian cell growth and mammalian cell transduction followed by nucleic acid-guided nuclease editing in live mammalian cells.

Abstract: Systems, methods and compositions provided herein relate to the preparation of nucleic acid libraries. Some embodiments include the preparation of nucleic acid libraries by ligation of single-stranded nucleic acids.

Abstract: Particular forward and reverse primers may be used to link distant regions of the same large DNA molecule into a smaller DNA molecule. A reverse primer R1 can have a first portion complementary to an ending sequence of region A and can have a second portion having an overlapping sequence. A forward primer F2 can have a first portion complementary to a starting sequence of region B, where the forward primer includes a complementary overlapping sequence (e.g., the same first portion or a second portion) that is complementary to the overlapping sequence. The first portion of F2 may be the entire primer. The smaller DNA molecules can be used to determine haplotypes of regions. Kits including the particular forward and reverse primers are also described.

Abstract: Polypeptides, such as antibody molecules and TCR molecules, and methods of making the same, are disclosed. The polypeptides can be used to treat, prevent, and/or diagnose disorders.

Abstract: Disclosed are methods of altering expression of a gene with a promoter region CTCF binding site. Also disclosed are compositions and methods useful for treating a disease or condition involving over-expression or under-expression of a gene with a promoter region CTCF binding site. Further disclosed are cells and non-human animals with modified a promoter region CTCF binding site, as well as methods for screening for compounds that can modify the expression of a gene with a promoter region CTCF binding site.

Abstract: RNA editing is achieved using oligonucleotide constructs comprising (i) a targeting portion specific for a target nucleic acid sequence to be edited and (ii) a recruiting portion capable of binding and recruiting a nucleic acid editing entity naturally present in the cell. The nucleic acid editing entity, such as ADAR, is redirected to a preselected target site by means of the targeting portion, thereby promoting editing of preselected nucleotide residues in a region of the target RNA which corresponds to the targeting portion.

Abstract: RNA molecules for RNA interference to target a mutant allele with a point mutation, wherein the molecule has a nucleotide sequence complementary to a nucleotide sequence of a coding region of the mutant allele; and when counted from the base at the 5?-end in the nucleotide sequence complementary to the sequence of the mutant allele: a base at position 5 or 6 is mismatched with a base in the mutant allele; a base at position 10 or 11 is at the position of the point mutation and is identical to the base at the position of the point mutation in the mutant allele; the group at the 2?-position of the pentose in the ribonucleotide at position 8 is modified with OCH3, halogen, or LNA; and the group at the 2?-position of the pentose in the ribonucleotide at position 7 is not modified with any of OCH3, halogen, and LNA.

Abstract: The invention provides an oligonucleotide comprising an inosine, and/or a nucleotide containing a base able to form a wobble base pair or a functional equivalent thereof, wherein the oligonucleotide, or a functional equivalent thereof, comprises a sequence which is complementary to at least part of a dystrophin pre-m RNA exon or at least part of a non-exon region of a dystrophin pre-m RNA said part being a contiguous stretch comprising at least 8 nucleotides. The invention further provides the use of said oligonucleotide for preventing or treating DMD or BMD.

Abstract: The invention relates to antisense oligonucleotides (AON) for use in the prevention, treatment, or amelioration of a corneal dystrophy caused by a (mutated) TGFBI gene. More specifically, the invention relates to gapmers for use in the downregulation of TGFBI mRNA expression and/or TGFBI protein expression, thereby preventing, treating, or ameliorating the TGFBI-related corneal dystrophy. The AONs of the present invention prevent or inhibit the occurrence of corneal deposits due to (mutated) TGFBI genes.

Abstract: Disclosed herein am compositions and methods for targeting a novel regulatory element of agene. The compositions may be used in methods of modifying growth of a cell, decreasing cell fitness, increasing cell fitness, and/or treating cancer such as leukemia.

Abstract: A method for ameliorating or treating a malignant tumor by administering a therapeutically effective amount of a formulation containing RNAi agents. A formulation for use in distributing RNAi molecules targeted to a human GST-? for treating a malignant tumor in a subject. The formulation may include nanoparticles composed of an ionizable lipid, a DSPE lipid, and additional lipids. A drug product may be made by lyophilization of the formulation.

Abstract: The present invention provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell.

Abstract: Provided are an RNA plasmid delivery system and an application thereof. The RNA plasmid delivery system comprises a plasmid carrying an RNA fragment required to be delivered; the plasmid can be enriched in an organ tissue of a host, and spontaneously forms an exosome containing the RNA fragment in the organ tissue of the host, and therefore can enter and be combined with a target tissue to deliver the RNA fragment into the target tissue. The RNA delivery system is safe, reliable, good in druggability, and strong in universality.

Abstract: A drug delivery for treating renal cancer, and in particular, clear cell renal carcinoma is provides. The drug delivery system includes a plurality of nanoparticles wherein each nanoparticle includes CD70-targeting peptides conjugated thereto and anti-HIF2? siRNAs conjugated thereto. A method for treating renal cancer is also provided.

Abstract: Disclosed herein are engineered oligonucleotides for selective inhibition of polypeptide expression and activity. Also disclosed herein are methods of selectively inhibiting polypeptide expression and activity contacting an engineered oligonucleotide with a polynucleotide encoding the polypeptide.

Abstract: An RNA delivery system for the treatment of Huntington's disease. The system comprises a viral vector, the viral vector carries RNA fragments capable of treating Huntington's disease, the viral vector is capable of enrichment in organ tissues of a host and endogenously and spontaneously forming a complex containing the RNA fragments capable of treating Huntington's disease in the organ tissues of the host, and the complex can deliver the RNA fragments into a target tissue to treat Huntington's disease. The safety and reliability of the RNA delivery system for the treatment of Huntington's disease have been fully verified. The system has good medicinal properties, strong versatility, and has economic benefits and application prospects.

Abstract: Provided herein are compositions and methods for reducing expression of C9orf72 transcripts in cells containing expanded intronic GGGGCC regions, including those in subjects having or at risk of developing amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).

Abstract: The present disclosure concerns isolated double stranded (ds) silencing RNA (siRNA) to target a backsplice junction between exons 12 and 7 in the MAPT gene. The ds siRNA include at least one nucleotide from the 3? terminus of exon 12 linked to at least one nucleotide of the 5? terminus of exon 7, thereby overlapping the backsplice junction. Targeting the junction ensure that that ds siRNA are limited in targeting the circular RNA produced by the backsplicing while allowing normal expression of the MAPT gene.

Abstract: Provided herein are methods for the treatment of polycystic kidney disease, including autosomal dominant polycystic kidney disease, using modified oligonucleotides targeted to miR-17.

Abstract: RNAi agents for inhibiting the expression of the alpha-1 antitrypsin (AAT) gene, compositions including AAT RNAi agents, and methods of use are described. Also disclosed are pharmaceutical compositions including one or more AAT RNAi agents together with one or more excipients capable of delivering the RNAi agent(s) to a liver cell in vivo. Delivery of the AAT RNAi agent(s) to liver cells in vivo inhibits AAT gene expression and treats diseases associated with AAT deficiency such as chronic hepatitis, cirrhosis, hepatocellular carcinoma, transaminitis, cholestasis, fibrosis, and fulminant hepatic failure.

Abstract: Disclosed herein are compositions and uses thereof for treating cancers.

Abstract: siRNA molecules and pharmaceutical compositions containing siRNA molecules are provided for inhibiting expression of KRAS, RAF1 and mutant KRAS peptides or proteins. Methods of treatment of cancer are provided in which the pharmaceutical compositions are administered to a subject in need thereof. The cancer may be lung, colon, or pancreatic cancers, including non-small cell lung cancer (NSCLC). Combinations of siRNAs, packaged in nanoparticles with co-polymer carriers and delivered simultaneously to target cells, elicit an additive or synergistic effect to inhibit tumorous cell growth.

Abstract: Provided herein are methods, compounds, and compositions for reducing expression of GYS1 in an individual. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate a glycogen storage disease or disorder in an individual in need.

Abstract: The subject invention pertains to a method for promoting axon regeneration in a subject with central nervous system injury. More specifically, the method comprises activating STAT1 signaling, cGAS-STING pathway, or a combination thereof by administering IFN? and inhibiting the expression or function Protein Tyrosine Phosphatase Non-Receptor Type 2 (PTPN2) inhibitor; or administering a STING agonist.

Abstract: The present disclosure provides a duplex or single-stranded siRNA molecule against plasminogen, the siRNA molecule containing modified or unmodified nucleotides and wherein at least one strand of the duplex or the single-stranded siRNA has a sequence that has at least 80% sequence identity to any one of SEQ NOs: 1 to 28. Further provided is a duplex or single-stranded siRNA molecule against plasminogen, the siRNA molecule containing modified or unmodified nucleotides and is between 25 and 35 nucleotides in length. The siRNA molecule may be formulated in a lipid nanoparticle as described herein.

Abstract: The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting a solute carrier family member gene, e.g., SLC30A10, or SLC39A8. The invention also relates to methods of using such RNAi agents to inhibit expression of a solute carrier family member gene, e.g., an SLC30A10 gene, or an SLC39A8 gene, and to methods of preventing and treating a solute carrier family member-associated disorder, e.g., a hypermanganesemia.

Abstract: The present invention is related to the field of genetic engineering. In particular, the repair, reversion and/or conversion of genetic mutations that are linked to a muscular dystrophy disease. Specifically contemplated are gene editor nuclease proteins or base editor proteins that are targeted to the muscular dystrophy genetic mutations or pathogenic variants. Such gene editor nuclease proteins include, but are not limited to Cas12a nuclease proteins and adenine base editor proteins. Repair, reversion and/or disruption of the genetic mutation or pathogenic variant reduces at least one symptom of a muscular dystrophy disease.

Abstract: An isolated or purified AON for modifying pre-mRNA splicing in the Receptor for Advanced Glycation End-products (RAGE) to modulate splicing of the RAGE gene transcript or part thereof is provided.