Abstract: This invention relates to variants of Cas12a nucleases having altered protospacer adjacent motif recognition specificity. The invention further relates to methods of making CRISPR-CAS nuclease variants and methods of modifying nucleic acids using the variants.

Abstract: This invention relates to variants of Cas12a nucleases having altered protospacer adjacent motif recognition specificity. The invention further relates to methods of making CRISPR-CAS nuclease variants and methods of modifying nucleic acids using the variants.

Abstract: Compositions and methods are provided for modulating growth of a genetically modified bacterial cell present in a human organ, for modulating growth of a genetically modified bacterial cell in an organ (e.g., gut), for displacing at least a portion of a population of bacterial cells in an organ, and for facilitating gut colonization by a genetically modified bacterial cell. Also provided are genetically modified bacterial cells, e.g., cells that include a heterologous carbohydrate-utilization gene or gene set that provides for the ability to utilize as a carbon source a rare carbohydrate of interest that is utilized as a carbon source by less than 50% of bacterial cells present in a human microbiome.

Abstract: The present disclosure provides methods for manufacturing a fXa derivative protein at large scale leading to high yield of highly pure protein product. The method may include adding a detergent to a sample that contains a polynucleotide construct encoding the protein and purifying the protein through a soybean trypsin inhibitor (STI)-based affinity chromatograph, an ion exchange and mixed mode chromatograph and a hydrophobic interaction.

Abstract: The disclosure provides a modified protein that is a combination of (i) an L-asparaginase and (ii) one or more (poly)peptide(s), wherein the (poly)peptide consists solely of proline and alanine amino acid residues, and methods of preparation and use thereof.

Abstract: The present disclosure relates to a carbonic anhydrase complex and a method for preparing same, in which a conjugate of a carbonic anhydrase and a dockerin module is bound to a small cellulose binding protein including a cohesin module and a cellulose binding module (CBM) and method of manufacturing thereof. The complex, which includes a cellulose binding module, is immobilized on the surface of green algae, to increase access to a substrate and enzyme activity, thereby efficiently fixing carbon dioxide, and increasing the growth and lipid production of green algae without adding other carbon sources. The present disclosure is expected to be actively utilized in fields, such as biofuels, using carbon dioxide fixation.

Abstract: Genetically engineered bacteria, pharmaceutical compositions thereof, and methods of modulating and treating diseases associated with hyperphenylalaninemia are disclosed.

Abstract: A system and method for controlling metabolic enzymes or pathways in cells to produce a chemical above the levels of a wild-type strain is disclosed. The system utilizes cells, including yeasts, bacteria, and molds, having at least two genes capable of being controlled bi-directionally with light, where one gene is turned from off to on when exposed to light and another gene is turned from on to off when exposed to light, the two genes reversing when the light is turned off. Cells may utilize any number of sequences that benefit chemical production, including sequences that: encode for constitutive transcription of light-activated transcription factor fusions; encode for a metabolic enzyme; encode for a repressor; induce expression of metabolic enzymes; and an endogenous or exogenous activator expressed by a constitutive promoter, inducible promoter, or gene circuit.

Abstract: The present invention provides engineered deoxyribose-phosphate aldolase polypeptides useful under industrial process conditions for the production of pharmaceutical and fine chemical compounds.

Abstract: The invention provides enzyme particles comprising an immobilized 1,3 specific lipase and a copolymer of styrene and divinylbenzene. The particles are suitable for enzymatic interesterification of triglycerides, and subsequent separation of the enzyme and triglycerides by filtration.

Abstract: Methods, devices, and systems for isolating nucleic acid e.g., in a point of need setting, featuring a housing with a binding chamber therein, the binding chamber comprising a binding component capable of binding nucleic acid or other molecule or biomolecule of interest, and at least one fluid chamber for housing a sample or other solutions such as but not limited to buffers fluidly connected to the binding chamber. The fluids in the fluid chamber can be conveyed to and from the binding chamber, for example with the use of an actuator.

Abstract: The invention relates to processes for purification of poly-tagged products, such as mRNA, from synthetic or biological compositions. The process involves contacting the composition with a oligo d (T)-functionalized chromatography medium comprising a convection-based chromatography material.

Abstract: The invention provides for systems, methods, and compositions for targeting and editing nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a DNA-targeting Cpf1 protein, at least one guide molecule, and at least one adenosine deaminase protein or catalytic domain thereof.

Abstract: The disclosure provides adenosine deaminases that are capable of deaminating adenosine in DNA. The disclosure also provides fusion proteins comprising a Cas9 (e.g., a Cas9 nickase) domain and adenosine deaminases that deaminate adenosine in DNA. In some embodiments, the fusion proteins further comprise a nuclear localization sequence (NLS), and/or an inhibitor of base repair, such as, a nuclease dead inosine specific nuclease (dISN).

Abstract: A method for constructing a multiplex PCR library for high-throughput targeted sequencing: first acquiring a targeted DNA product by means of a high-specificity multiplex PCR reaction, and then digesting with a specific endonuclease, such that a specific molecular barcode is produced at the tail end of the PCR product; thus, the library construction process is more efficient, and the accuracy and sequencing depth of the obtained data are also ensured.

Abstract: Methods for the automated template-free synthesis of user-defined sequence controlled biopolymers using microfluidic devices are described. The methods facilitate simultaneous synthesis of up to thousands of uniquely addressed biopolymers from the controlled movement and combination of regents as fluid droplets using microfluidic and EWOD-based systems. In some forms, biopolymers including nucleic acids, peptides, carbohydrates, and lipids are synthesized from step-wise assembly of building blocks based on a user-defined sequence of droplet movements. In some forms, the methods synthesize uniquely addressed nucleic acids of up to 1,000 nucleotides in length. Methods for adding, removing and changing barcodes on biopolymers are also provided. Biopolymers synthesized according to the methods, and libraries and databases thereof are also described. Modified biopolymers, including chemically modified nucleotides and biopolymers conjugated to other molecules are described.

Abstract: The present disclosure provides mammalian cell lines for expression of viral vectors, and methods of making and using the same. Provided methods employ use of identifiers that are capable of being packaged into a viral vector to select and/or identify mammalian cell lines with engineered sequences associated with beneficial characteristics for viral vectors production. Exemplary viral vectors include AAV vectors.

Abstract: Provided in some aspects are methods for light-controlled in situ surface patterning of a substrate comprising a step of blocking or ablating oligonucleotide molecules in a boundary region separating a plurality of spot regions, and attaching oligonucleotides to oligonucleotide molecules in a first one or more of the spot regions.

Abstract: The present invention falls within the field of biotechnology, and specifically discloses a method for constructing a cyclized library and a ring-forming linker. The method comprises: 1) breaking a DNA sequence into fragments; 2) enabling two ends of the broken fragment to form 3? end protrusions; and 3) cyclizing the fragment with 3? end protrusions to form a ring-shaped library by means of a ring-forming linker, wherein the ring-forming linker is a double chain which is not completely paired and has 3? end protrusion at both ends, and the 3? end protrusion of the ring-forming linker is complementary to the 3? end protrusion of the broken fragment. According to the present invention, an A-sticky end of the end is formed by means of repairing the end of and the adding A to the broken DNA fragment, and same is then complementary to the specifically designed linker T sticky end to form a cyclized structure, and the connection at the gap is completed under the action of a ligase.

Abstract: Methods and compositions are provided herein for preparing high-throughput cDNA sequencing libraries.

Abstract: Methods for producing a linear deoxyribonucleic acid (DNA) product with enhanced resistance to nuclease digestion are provided. The methods comprise: (a) contacting a double-stranded DNA molecule with an endonuclease, a ligase and first and second adaptor molecules to form a single contiguous aqueous volume; and (b) incubating the single contiguous aqueous volume to generate a linear DNA product. There are also provided linear deoxyribonucleic acid (DNA) products with enhanced resistance to nuclease digestion and uses thereof.

Abstract: Described herein are methods of modifying a target gene in a patient or in a patient-derived cell, wherein the patient has an autosomal recessive disorder with compound heterozygous mutations, the methods including delivering a first modified guide RNA, a second modified guide RNA, a Cas9 polypeptide, a biotin-binding molecule, a first biotinylated donor polynucleotide, and a second biotinylated donor polynucleotide. The first modified guide RNA and the first biotinylated donor polynucleotide correct a first diseased allele, and the second modified guide RNA and the second biotinylated donor polynucleotide correct a second diseased allele.

Abstract: Provided herein are chemically ligated guide RNA oligonucleotides (LgRNA) which comprises one or more internal non-nucleotide chemical linkers (nNt-linker), their complexes with CRISPR-Cas protein, and their uses for LgRNA-directed CRISPR gene editing. Also disclosed are processes and methods for preparation of these compounds.

Abstract: This disclosure provides systems, methods, and compositions for site-specific genetic engineering using Programmable Addition via Site-Specific Targeting Elements (PASTE). PASTE comprises the addition of an integration site into a target genome followed by the insertion of one or more genes of interest or one or more nucleic acid sequences of interest at the site. PASTE combines gene editing technologies and integrase technologies to achieve unidirectional incorporation of genes in a genome for the treatment of diseases and diagnosis of disease.

Abstract: The present invention relates to a novel-structured nucleic acid complex having a blood-brain barrier penetration ability and a composition comprising same and, more specifically, to a nucleic acid complex in which a bioactive nucleic acid is complementarily bound to a carrier peptide nucleic acid modified to be generally positively charged, and to a composition for blood-brain barrier penetration comprising same. The nucleic acid complex according to the present invention can penetrate the blood-brain barrier at excellent efficiency, and especially, the conjugation of a drug into the nucleic acid complex increases the blood-brain barrier penetration ability of the drug, and thus is very useful in treatment or diagnosis of diseases.

Abstract: The present invention relates to RNAi agents, e.g., double stranded RNAi agents, targeting the Kallikrein B, Plasma (Fletcher Factor) 1 (KLKB1) gene, the Factor XII (Hageman Factor (F12) gene, or the Kininogen 1 (KNG1) gene, and methods of using such RNAi agents to inhibit expression of a KLKB1 gene, an F12 gene, and/or a KNG1 gene, and methods of treating subjects having an hereditary angioedema (HAE) and/or a contact activation pathway-associated disorder.

Abstract: Regulatory elements that drive Schwann cell-specific gene expression, nucleic acid vectors, virus particles, and therapeutic compositions incorporating these constructs; and methods of using these various compositions to alter gene expression in a Schwann cell or to treat a subject having a condition associated with misexpression or insufficient function of a target gene in Schwann cells.

Abstract: Disclosed herein are methods of increasing or decreasing endogenous interferon amounts in subjects which comprise inhibiting, reducing, increasing, enhancing, or stabilizing MORC3 in the subjects.

Abstract: The present invention disclosed an application of an antisense oligonucleotide targeting a PBX1 promoter region G-quadruplex in a preparation of a medicine for treating melanoma. The medicine for treating melanoma has one or more of following uses: inhibiting the proliferation of melanoma cell; inhibiting the migration of melanoma cell; inhibiting the invasion of melanoma cell; inhibiting the growth of melanoma; and inhibiting the lung metastasis of melanoma. The identification of the antisense oligonucleotide targeting the PBX1 promoter region G-quadruplex provided by the present invention provides a new drug target and new treatment methods and ideas for the development of a new generation of inhibiting melanoma medicines.

Abstract: The invention relates to inhibitory nucleic acids and rAAV-based compositions, methods and kits useful for treating Amyotrophic Lateral Sclerosis.

Abstract: A composition for treating sickle cell disease includes a cGMP exosome having a size range between 60 nm to 120 nm, which may be extracted from a human mesenchymal stem cell (hMSC) or human PBMC at 320,000 g, wherein the cGMP exosome may be loaded with a Hemoglobin Subunit Beta (HBB) DNA plasmid carrying a gene encoding a normal beta chain of hemoglobin and alone or in combination with a short interference RNA (siRNA) that silences the translation of the SNP rs334 (A) mutation of the beta chain of a Hemoglobin A protein.

Abstract: Antisense polynucleotides and their use in pharmaceutical compositions to induce exon skipping in targeted exons of the gamma sarcoglycan gene are provided, along with methods of preventing or treating dystrophic diseases such as Limb-Girdle Muscular Dystrophy.

Abstract: A composition of matter comprising a DNAzyme molecule capable of mediating cleavage of p21 mRNA corresponding to SEQ ID NO: 1, wherein said DNAzyme molecule comprises a nucleic acid sequence at least 80% identical to the nucleic acid sequence set forth in any one of SEQ ID NOs: 23, 29, 33-38, 40, 42, 45-48, 53-60, 63-65, 69-74 or 78, is disclosed. Methods of eradicating senescent cells or cancer cells, as well as methods of treating senescence-associated diseases or disorders, cancer, and fibrotic diseases and disorders are also disclosed.

Abstract: The present invention relates to a double-helix oligonucleotide construct comprising a double-stranded miRNA and a composition for preventing or treating cancer comprising the same. More particularly, the present invention relates to a double-helix oligonucleotide construct comprising miR-544a characterized by a method that effectively inhibits the proliferation of cancer cells or induces a voluntary death of cancer cells, and an anticancer composition comprising the construct.

Abstract: The present invention refers to immunosuppression-reverting oligonucleotides comprising 12 to 18 nucleotides, wherein at least one of the nucleotides is modified, and the oligonucleotide hybridizes with an hybridizing active region of the nucleic acid sequence of an ectoenzyme (CD73) of SEQ ID NO.1 (human) and/or SEQ ID NO.2 (human). The invention is further directed to a pharmaceutical composition comprising such oligonucleotide. The oligonucleotide and the pharmaceutical composition are used in a method of preventing and/or treating a disorder, where a CD73 imbalance is involved.

Abstract: The present disclosure provides methods of treating patients having decreased bone mineral density, methods of identifying subjects having increased risk of developing decreased bone mineral density, methods of detecting human Zinc And Ring Finger 3 (ZNRF3) variant nucleic acid molecules and variant polypeptides, and ZNRF3 variant nucleic acid molecules and variant polypeptides.

Abstract: The present embodiments provide methods, compounds, and compositions useful for inhibiting PNPLA3 expression, which may be useful for treating, preventing, or ameliorating a disease associated with PNPLA3.

Abstract: The present embodiments provide methods, compounds, and compositions useful for inhibiting PNPLA3 expression, which may be useful for treating, preventing, or ameliorating a disease associated with PNPLA3.

Abstract: Disclosed are polynucleotides, compositions, and methods related to RNA interference (RNAi). The disclosed polynucleotides, compositions, and methods may be utilized for treating diseases and disorders through RNAi. Particular disclosed are toxic RNAi active seed sequences and methods of using toxic RNAi active sequences for killing cancer cells. The disclosed toxic RNAi active seed sequences preferentially target and inhibit the expression of multiple essential genes for cell survival and/or growth through a process called “death-induced by survival gene elimination” or “DISE.

Abstract: Disclosed herein are compositions and methods comprising epigenetic editors for epigenetic editing or cells, nucleic acids, and vectors comprising the same. Also disclosed are epigenetically modified chromosomes.

Abstract: Disclosed are treatment means, compositions of matter and protocols useful for suppression of acute respiratory disorder (ARDS) through induction of RNA interference in the pulmonary microenvironment alone and/or in conjunction with mucolytic and/or DNA disrupting agents. In one embodiment short interfering RNA (siRNA) is prepared which targets complement receptors C3R and/or C5R together with TNF-receptor, IL-6 receptor and/or TLR4 and TLR9. In some embodiments nanostilbene is utilized as a delivery vehicle for siRNA delivery.

Abstract: The present invention relates to an aptamer not binding to the receptor-binding domain of the SARS-CoV-2 spike glycoprotein nor inhibiting the interaction of the receptor-binding domain (RED) of spike glycoprotein with angiotensin-converting enzyme II (ACE2) and/or comprising or consisting of a nucleotide sequence SEQ ID NO: 1, a composition comprising the aptamer, and the use of the aptamer in the detection of SARS-CoV-2 or diagnosis or treatment of a SARS-CoV-2 infection.

Abstract: Compositions and methods for stimulating toll-like receptor 9 (TLR9) are provided. More particularly, immunostimulatory oligonucleotides, methods of enhancing immunostimulatory properties of oligonucleotides, and methods of eliciting immune responses are disclosed herein.

Abstract: The present invention relates to the field of biotechnologies and in particular to a nucleotide sequence having promoter activity of the transcription in prokaryotic and eukaryotic cell systems.

Abstract: Transgenic INIR20 soybean plants comprising modifications of the MON87701 soybean locus which provide for facile excision of the modified MON87701 transgenic locus or portions thereof, methods of making such plants, and use of such plants to facilitate breeding are disclosed.

Abstract: Transgenic INIR19 soybean plants comprising modifications of the DAS81419 soybean locus which provide for facile excision of the modified DAS81419 transgenic locus or portions thereof, methods of making such plants, and use of such plants to facilitate breeding are disclosed.

Abstract: Materials and methods for creating canola (e.g., Brassica napus) lines having oil with increased oleic acid content are provided herein. For example, a Brassica plant, plant part, or plant cell having an induced mutation in one or more FAD2 gene copies, oil produced from the plant, plant part, or plant cell has increased oleic acid content and decreased linolenic acid content as compared to oil produced from a corresponding wild type Brassica plant, plant part, or plant cell, wherein the mutation was induced by one or more rare cutting endonucleases targeted to the one or more FAD2 gene copies, and methods of making and using the Brassica plant, plant part or plant cell, are provided.

Abstract: The present disclosure provides methods of producing plants with preferred levels of cell wall biosynthesis; and uses of such plants. The inventors have identified that the GFR9, CCoAOMT and MYB41 genes are major regulators of the cell wall biosynthesis pathway. Plants with modulated cell wall biosynthesis, based on modulation of the expression or activity of the GFR9, CCoAOMT and MYB41 genes, have divergent uses including pulp and paper production, and bioproduct production.

Abstract: The subject invention relates in part to the surprising discovery that Cry1Da is active against corn earworm (CEW), Helicoverpa zea (Boddie). Methods for using Cry1Da in transgenic plants to prevent serious crop damage is described. Leaf and silk bioassays using transgenic maize expressing full length, core toxin region or chimeric Cry1Da demonstrated good insect protection against CEW larvae damage.

Abstract: Compositions and methods for controlling pests are provided. The methods involve transforming organisms with a nucleic acid sequence encoding an insecticidal protein. In particular, the nucleic acid sequences are useful for preparing plants and microorganisms that possess insecticidal activity. Thus, transformed bacteria, plants, plant cells, plant tissues and seeds are provided. Compositions are insecticidal nucleic acids and proteins of bacterial species. The sequences find use in the construction of expression vectors for subsequent transformation into organisms of interest including plants, as probes for the isolation of other homologous (or partially homologous) genes. The pesticidal proteins find use in controlling, inhibiting growth or killing Lepidopteran, Coleopteran, Dipteran, fungal, Hemipteran and nematode pest populations and for producing compositions with insecticidal activity.