Abstract: The present disclosure pertains to methods of activating TFEB independent of mTORC1 activity, methods of activating TFEB by enhancing GABARAP/FNIP/FLCN complex localization at an intracellular membrane surface, methods of characterizing a TFEB activating agent, and methods of treating a TRPML1-associated disease, disorder or condition, and compositions for use in said methods.

Abstract: Oligonucleotides and compositions including the same are disclosed for inhibiting or reducing apolipoprotein C-III (APOC3) gene expression. Methods of making and using the oligonucleotides also are disclosed, particularly uses relating to treating diseases, disorders and/or conditions associated with APOC3 expression.

Abstract: Isolation or in vitro assembly of the Cas9-crRNA complex of the Streptococcus thermophilus CRISPR3/Cas system and use for cleavage of DNA bearing a nucleotide sequence complementary to the crRNA and a proto-spacer adjacent motif. Methods for site-specific modification of a target DNA molecule in vitro or in vivo using an RNA-guided DNA endonuclease comprising RNA sequences and at least one of an RuvC active site motif and an HNH active site motif; for conversion of Cas9 polypeptide into a nickase cleaving one strand of double-stranded DNA by inactivating one of the active sites (RuvC or HNH) in the polypeptide by at least one point mutation; for assembly of active polypeptide-polyribonucleotides complex in vivo or in vitro; and for re-programming a Cas9-crRNA complex specificity in vitro and using a cassette containing a single repeat-spacer-repeat unit.

Abstract: The present disclosure provides recombinant microalgae that can deliver both pathogen protection and essential nutrition to honey bees. The microalgae can contain genetic modifications that result in the expression of RNA-interference (RNAi) inducing elements that target honey bee pathogens and endogenous honey bee genes.

Abstract: The present disclosure relates methods and compositions useful for prevention of porcine reproductive and respiratory syndrome virus (PRRSv) in animals, including animals of the species Sus scrofa. The present teachings relate to swine wherein at least one allele of a CD163 gene has been inactivated, and to specific methods and nucleic acid sequences used in gene editing to inactivate the CD163 gene. Swine wherein both alleles of the CD163 gene are inactivated are resistant to porcine reproductive and respiratory syndrome virus (PRRSv).

Abstract: Compositions and methods for binding to a target sequence of interest are provided. Compositions include fusion proteins between DNA binding proteins or protein domains and nucleic acid modifying proteins or protein domains. The compositions find use in cleaving or modifying a target sequence of interest, visualization of a target sequence of interest, and modifying the expression of a sequence of interest. Compositions comprise RNA-guided nuclease polypeptides, CRISPR RNAs, trans-activating CRISPR RNAs, guide RNAs, deaminases, and nucleic acid molecules encoding the same. Vectors and host cells comprising the nucleic acid molecules are also provided. Further provided are CRISPR systems for binding a target sequence of interest, wherein the CRISPR system comprises an RNA-guided nuclease polypeptide and one or more guide RNAs. Also provided are deaminases which may be fused to a DNA-binding polypeptide and may be useful for gene editing.

Abstract: The present invention relates to a suppressor or inhibitor of (long interspersed element 1) LINE1 (L1) expression for medical use.

Abstract: A synthesis method of a targeted drug nCoVshRNA.2ACE2 of a COVID-19 virus, which includes the following steps: designing a consensus RNAi sequence siRNA of the COVID-19 virus and a variant strain thereof; synthesizing two complementary siRNAs into a small hairpin-shaped shRNA with a loop, and synthesizing ACE2 or a cell penetrating peptide ACE2 with a receptor-binding domain (RBD) as a ligand; and ligating the ACE2 to a sense strand and an antisense strand of the shRNA separately to synthesize the nCoVshRNA.2ACE2 including a shRNA region and an ACE2 region. The bivalent ACE2 functions to neutralize the RBD and deliver the shRNA in a targeted manner; an “shRNA-ACE2-RBD-virus” complex bridged by the ACE2 allows the shRNA to enter target cells with virus infection, thereby avoiding a side effect of non-specific delivery of the shRNA to uninfected cells, as well as resisting the variant strain and neutralizing the virus with the ACE2.

Abstract: Compositions, systems, kits, and methods are described herein for the modulation, and in particular the reduction or inhibition, of expression of the FLCN gene or the activity of FLCN protein in a cell, animal, or human subject. Compositions, systems, and methods disclosed herein can be used to prevent, ameliorate, or treat diseases, particularly neuromuscular or neurodegenerative diseases, retinal degeneration diseases, or other TDP-43 proteinopathies. Methods are described for the modulation, and in particular the reduction or inhibition of FLCN expression or activity, comprising the use of a modulator to regulate FLCN expression or activity. Methods are also described for the development, synthesis, and production of modulators, and for therapeutic treatment of TDP-43 proteinopathies such as ALS and other related disorders.

Abstract: Provided is a small RNA, a composition comprising the small RNA, a method for using same and use of same. The small RNA or composition can inhibit the ability of any one or more of pathways or genes listed in Table 3, or decrease or down regulate the expression level of IL-1 beta, IL-6, and/or TNF-alpha in vitro or in vivo, or treat or prevent IL-1 beta, IL-6, and/or TNF-alpha related diseases and/or increase cell viability in a subject.

Abstract: An antisense oligonucleotide is provided which induces exon skipping in ACE2 gene. An antisense oligonucleotide of 15-30 bases or a salt or a solvate thereof, wherein the antisense oligonucleotide has a nucleotide sequence complementary to a target site in exon 18 of angiotensin-converting enzyme 2 gene and is capable of inducing exon skipping in angiotensin-converting enzyme 2 gene. A pharmaceutical drug comprising the antisense oligonucleotide or a salt or a solvate thereof; and an agent for inhibiting the expression of angiotensin-converting enzyme 2 protein and/or for enhancing the expression of soluble angiotensin-converting enzyme 2.

Abstract: Aerobic microbial processes comprise culturing microbes comprising a (per)chlorate respiration pathway in a bioreactor in a bioprocess employing microbial respiration of chloroxyanions as a source of oxygen for the bioprocess, in the absence of external addition of molecular oxygen.

Abstract: Disclosed herein are flavivirus signal peptide mutants useful for enhancing the production and secretion of flavivirus envelope (E) viral proteins or virus-like proteins. Also disclosed herein are methods of vaccinating subjects (e.g.

Abstract: The present invention relates to stabilization of RNA, in particular mRNA, and an increase in mRNA translation. The present invention particularly relates to a modification of RNA, in particular in vitro-transcribed RNA, resulting in increased transcript stability and/or translation efficiency. According to the invention, it was demonstrated that certain sequences in the 3?-untranslated region (UTR) of an RNA molecule improve stability and translation efficiency.

Abstract: The inventive subject matter includes an antimicrobial peptide vectored composition made of a bacterial protein expression vehicle expressing one or more recombinant antimicrobial peptide effector molecules. More specifically these novel recombinant antimicrobial peptide effector molecules exhibit preferential anti¬microbial activity. The utility of the current inventive subject matter has demonstrated a reduced viability of Eimeira acervulina sporozoites in vitro using a sporozoite killing assay. More specifically, the antimicrobial peptide vectored composition is a bacterial protein expression vehicle expressing one or more recombinant antimicrobial peptide effector molecules, wherein the one or more recombinant antimicrobial peptide effector molecules are engineered from a NK-lysin gene and the one or more recombinant antimicrobial peptide effector molecules are engineered to express functionally active NK-2.

Abstract: A method of expressing an agronomically or non-agronomically beneficial trait in a plant plastid comprising expressing an exogenous nucleic acid in the plant to produce non-photosynthetic mutant plants, and using callus grown from the mutant plants as recipients for introduction of a construct having a functional copy of the mutated gene and a gene conferring an agronomically or non-agronomically beneficial trait. Embodiments provide for mutations in chloroplast-encoded genes, as well as mutations in nuclear-encoded genes targeted to the chloroplast that are required for photosynthesis, plants and plant parts produced from such methods, as well as kits for performing the methods as described.

Abstract: The invention provides recombinant DNA molecules and constructs, as well as their nucleotide sequences, useful for modulating gene expression in plants. The invention also provides transgenic plants, plant cells, plant parts, and seeds comprising the recombinant DNA molecules operably linked to heterologous transcribable DNA molecules, as are methods of their use.

Abstract: This disclosure concerns compositions and methods for increasing the expression of a polynucleotide of interest. Some embodiments concern novel transactivation polypeptides and variants thereof that have been identified in plants, and methods of using the same. Particular embodiments concern the use of at least one DNA-binding polypeptide in a fusion protein to target at least one transactivation polypeptide or variant thereof to a specific binding site on a nucleic acid comprising the polynucleotide of interest, such that its expression may be increased.

Abstract: The present disclosure provides a heat-stress related gene ZmHsf11 and an application of the gene in regulating heat resistance of plants. The present disclosure belongs to the field of biotechnology. The present disclosure reports for the first time a heat resistance negative regulation related gene ZmHsf11 and its protein. In the present invention, it is found that the expression of ZmHsf11 gene can be induced by adverse stresses such as high temperatures. By overexpressing the gene in rice and identifying functions of the gene, it is found that a survival rate of the overexpressed rice plant under the heat treatment is significantly reduced after overexpression. By identifying functions of the ZmHsf11 mutant plant obtained in the present invention, the heat resistance of the mutant plant is significantly increased after the heat treatment.

Abstract: Compositions and methods for enhancing the resistance of plants, particularly wheat and triticale plants to stem rust caused by Puccinia graminis f. sp. tritici are provided. The compositions comprise nucleic acid molecules encoding resistance (R) gene products and variants thereof and plants, seeds, and plant cells comprising such nucleic acid molecules. The methods for enhancing the resistance of a plant to stem rust comprise introducing a nucleic acid molecule encoding an R gene product into a plant cell. Additionally provided are methods for using the resistant plants in agriculture to limit stem rust.

Abstract: Disclosed herein are plant-based, molecular and diagnostic tools that can be used to block aphid transmission of poleroviruses, including stabilized proteins for expression in transgenic plants and/or in formulations for direct plant delivery. Further disclosed are proteins that can kill aphids and methods to produce these proteins. Antibodies and useful for diagnostic and therapeutic uses against poleroviruses.

Abstract: The invention discloses a plant thermo-sensitive male sterile gene mutant tms15 and uses thereof. The nucleotide sequence of the plant thermo-sensitive male sterile gene mutant tms15 is SEQ ID No. 1. The inventor screened the thermo sensitive genic male sterile mutant tms15 by EMS mutagenesis of Zhonghua 11, which showed a male sterile phenotype under high temperature conditions (>28° C.) and restored fertility under low temperature conditions (22˜24° C.). The cytological results shows that the sporogenous cells in tms15 plants proliferated excessively and the tapetum cells are also vacuolized abnormally under high temperature. The normal proliferation of sporogenous cells and the normal development of tapetal cells are restored to some extent after low temperature treatment.

Abstract: The present disclosure is in the field of genome engineering, particularly targeted genetic modification of a CISH gene.

Abstract: The present application relates to a method and system for delivering a nucleic acid. In particular, the present application relates to a method and system for expressing exogenous RNA and/or exogenous proteins by nucleic acid delivery. The present application provides a composition, including single-stranded DNA and at least one transfection reagent. A mass ratio of the single-stranded DNA to the transfection reagent in the composition is about 100 to about 0.1. The present invention further provides a method and system for delivering a nucleic acid using the composition.

Abstract: The present disclosure relates to the technical field of biomedicine, in particular to use of circUTRN in preparation of a drug for treating heart failure, a recombinant vector, and a drug for treating heart failure. It is proved by experiments that the drug for treating heart failure prepared by the circUTRN is capable of treating or ameliorating the heart failure, and especially has a desirable therapeutic effect on the heart failure caused by ischemia-reperfusion injury (IRI). Specifically, the circUTRN is capable of improving cardiac systolic dysfunction induced by myocardial IRI 3 weeks. In addition, the circUTRN is also capable of reducing an infarct size of acute myocardial IRI; and overexpression of the circUTRN can inhibit cardiomyocyte apoptosis induced by oxygen-glucose deprivation/recovery.

Abstract: The present invention relates to the development of a method for the manufacturing of LVV vectors in a packed bed bioreactor by multi-plasmid transient DNA transfection. More particularly, the present invention discloses and claims a process in which steps applied in perfusion or in batch mode are combined to obtain an effective process. Moreover, the invention identifies an effective range of total DNA to be successfully used in the step of transient transfection in a packed bed bioreactor for the manufacturing of lentiviral vectors.

Abstract: Provided herein are nucleic acid molecules, vectors, and recombinant AAV comprising an inducible gene expression system. The system includes a transgene encoding a gene product operably linked to expression control sequences comprising a promoter; an activation domain comprising a canine or feline transactivation domain and a FKBP12-rapamycin binding (FRB) domain of canine or feline FKBP12-rapamycin-associated protein (FRAP); a DNA binding domain comprising a zinc finger homeodomain (ZFHD) and one, two or three FK506 binding protein domain (FKBP) subunit genes; and at least 8 copies of the binding site for ZFHD (8XZFHD) followed by a minimal IL2 promoter. The presence of an effective amount of a rapamycin or a rapalog induces expression of the transgene in a host cell.

Abstract: Provided herein are recombinant viruses and artificially coated delivery systems, and methods of use.

Abstract: A recombinant measles viral vector comprising a nucleic acid sequence encoding a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike glycoprotein is provided. Polypeptides comprising the SARS-CoV-2 spike glycoprotein also are provided, as well as related nucleic acids, vectors, and compositions. The polypeptides, nucleic acids, vectors, and compositions can be used in methods of preventing, inhibiting, reducing, eliminating, protecting, or delaying the onset of an infection or an infectious clinical condition caused by coronavirus and methods for inducing an immune response against a coronavirus.

Abstract: Provided herein is a gene therapy for GLUT1 Deficiency Syndrome and related disorders using a recombinant adeno-associated virus (rAAV) virion as a vector to express an GLUT1 protein or functional variant thereof. The rAAV virion may use an endothelial-specific promoter, e.g., a FLT-1 or Tie-1 promoter. The capsid may be an AAV6, AAV8, AAV9, AAVrh.74, or AAVrh.10 capsid or a functional variant thereof. Other promoters or capsids may be used. Further provided are methods of treatment, such as by intracerebrally and/or intravenously of the rAAV virion, and other compositions and methods.

Abstract: This invention comprises: compositions comprising a derivative, plasmids, a reagent kit and methods of making these compositions a derivative, vaccine- and non-vacicine-compositions of above for causing death of cancer cells that form part of a tunoour and virus infected Denguue, Measles and other diseased cells; the derivative comprising replicating as well as non-replicating dervivaties of an attenuated negative stranded RNA virus belonging to family paramyxoviridae, including Measles Virus, comprising a single additional transcriptional unit carrying either only one or two or more non-viral genes, and the non-replicating derivatives being free from contaminating replicating Measles Virus (b) a Measles Virus packaging cell line for making above compositions, expressing the M, F and H proteins of MV stably. And (c) a reagent kit for producing the Measles Virus derivatives describved above.

Abstract: A method of correcting singletons in a selected AAV sequence in order to increasing the packaging yield, transduction efficiency, and/or gene transfer efficiency of the selected AAV is provided. This method involves altering one or more singletons in the parental AAV capsid to conform the singleton to the amino acid in the corresponding position(s) of the aligned functional AAV capsid sequences.

Abstract: The instant specification provides for evolved base editors which overcome deficiencies of those in art (including increased efficiency and/or decreased requirement for specific sequence-context at an editing site) and which are obtained a result of a phage-assisted continuous evolution (PACE) system. In particular, the instant specification provides for evolved cytidine base editors (e.g., based on APOBEC1, CDA, or AID cytidine deaminase domains) which overcome deficiencies of those in art (including increased efficiency and/or decreased requirement for specific sequence-context at an editing site) and which are obtained a result of a phage-assisted continuous evolution (PACE) system.

Abstract: The method of preparing polyethyleneimine-lipid nanoparticles (PEI-LNPs) for transfecting stem cells includes the following steps: S1, adding anhydride to a PEI solution to produce polycarboxylic acid; S2, dissolving the PEI-LNPs from S1, together with DPPC, DPPG, DPPE-PEG-COOH and cholesterol in chloroform, dissolving cGAMP in a water and then adding to such chloroform solution, and performing vacuum evaporation to remove the chloroform; S3, adding PBS for hydration, and performing ultrasonication to obtain liposomes; and S4, adding EDC/NHS to the liposome solution obtained for reaction for 15 min, then adding mRNA, and stirring the mixed solution to obtain a bionic virus nanovaccine. The prepared PEI-LNPs are used for delivering an mRNA vaccine and transfecting stem cells, wherein through a lipid PEI derivative library synthesized based on short-branched PEI with a variable length and hydrophobic tail substitution ratio, short-branched PEI can form a stable complex with the mRNA vaccine.

Abstract: The present disclosure pertains to methods and devices for delivering a compound into a cell, including passing a cell suspension through a surface containing pores, wherein the pores deform the cell thereby causing a perturbation of the cell such that the compound enters the cell, wherein the cell suspension is contacted with the compound.

Abstract: Disclosed herein are methods and compositions for treating muscular dystrophies, including DMD, by deleting and optionally replacing disease associated mutations in the genome of muscular dystrophy patients.

Abstract: Provided herein are cells with a gene modification of an ABO gene, RHD gene, and/or FUT1 gene. In some embodiments, the cells express reduced levels of a MHC I antigen and/or a MHC II antigen. In some instances, the cells are also hypoimmunogenic cells.

Abstract: Methods and compositions for modulating a target genome are disclosed.

Abstract: Some embodiments of the methods and compositions provided herein include preparing modified B cells. In some embodiments, an endogenous beta-2 microglobulin (B2M) gene in a B cell is modified. Some embodiments relate to increasing the resistance of modified B cells to killing by allogeneic immune cells. In some embodiments, the endogenous B2M gene is inactivated increasing the resistance of the modified B cell to killing by allogeneic immune cells. In some embodiments, a replacement MHC-I is inserted into an inactivated endogenous B2M gene increasing the resistance of the modified B cell to killing by allogeneic immune cells. Some embodiments include enriching for successfully modified cells.

Abstract: Provided herein are double strand DNA molecules comprising inverted repeats, expression cassette and one or more restriction sites for nicking endonucleases, the methods of use thereof, and the methods of making therefor.

Abstract: The invention relates to a composition for enhancing utrophin expression in cell by inducing mutations within a target sequence comprising a utrophin repressor binding site using a gene editing enzyme and the use thereof for the treatment of a dy-strophinopathy.

Abstract: Genome editing tools for use in systems designed to deliver large genetic elements are disclosed herein. A genome editing system is described, which includes i) an R2 element enzyme or other non-LTR site specific retrotransposon element and ii) a payload RNA, wherein the payload RNA comprises an insertion region and optionally one or more of a 5? homology region, a 3? homology region, and a protein binding element, wherein the insertion region comprises a template for a small or large nucleic acid insertion into the genome, and wherein the R2 element enzyme or other non-LTR site specific retrotransposon element comprises a targeting domain, a reverse transcriptase domain, and a nickase domain. Also disclosed are cells edited using such a genome editing system, methods for editing a genome, and compositions comprising cells edited with this genomic editing system.

Abstract: This disclosure provides novel integrases for site-specific genetic engineering. Also provided are systems, methods, and compositions for site-specific genetic engineering using Programmable Addition via Site-Specific Targeting Elements (PASTE) with the novel integrases.

Abstract: Disclosed are an expression cassette for isopropanol production, a recombinant vector for isopropanol production including the expression cassette, a recombinant microorganism for isopropanol production into which the vector is introduced, and a method of producing isopropanol using the recombinant microorganism. The recombinant microorganism in which a succinic acid bypass metabolic pathway is introduced to an isopropanol production pathway has very high ability to produce isopropanol. The recombinant microorganism is capable of producing isopropanol in an amount corresponding to about 100 times the maximum amount of isopropanol that is produced using known Corynebacterium glutamicum, and thus can effectively produce isopropanol and can be useful in various industrial fields where isopropanol is utilized.

Abstract: Methods of and system for growing and maintaining an optimized/ideal active yeast solution in the yeast tank and fermenter tank during the fermentation filling cycle are provided. A new yeast stage tank is used between the yeast tank and the fermenter tank allowing yeast to rapidly produce a huge amount of active young yeast cells for a fermenter during the filling period. A measurable and useful controlling factor, % DT/% Yeast by weight ratio (or “food” to yeast ratio), is used (e.g., % DT=glucose), which offers information on the health status of the yeast. The controlling factor is used to control the status of the yeast throughout the entire process.

Abstract: Provided herein are production systems and methods to produce a plurality of organic carbon-containing compounds from carbon dioxide, including glyceraldehyde 3-phosphate, glucose, cellulose, and starch, using stabilized enzymes in aqueous media.

Abstract: The present invention relates to a method for the recombinant production of olivetolic acid (OA) in a host species selected from amoebozoa, based on a hybrid-gene or enzyme of polyketide synthase 37 (PKS37) in which the C-terminal type III PKS domain from an amoeba is replaced by an olivetol synthase (OLS) from a plant, and is expressed together with an olivetolic acid cyclase from a multi-gene expression vector. Further provided is a recombinant amoebozoa host species, and an improved method for producing ?9-tetrahydrocannabinol (THC) or other cannabinoids.

Abstract: The present disclosure provides an engineered microorganism capable of producing malonic acid, malonate, esters of malonic acid, or mixtures thereof. The engineered microorganism includes a malonate-semialdehyde dehydrogenase that is heterologous to a native form of the engineered microorganism and comprises at least 80% sequence identity to SEQ ID NO: 6, wherein the engineered microorganism is capable of producing about 3 g/L to about 250 g/L of malonic acid, malonate, esters of malonic acid, or mixtures thereof.

Abstract: A protein variant having an L-tyrosine exporting activity, a microorganism expressing the same, and use thereof.

Abstract: The present invention provides a 5-methylfolate producing microorganism which a) has been modified to have a decreased expression and/or activity of a polypeptide having both dihydrofolate synthase activity and folylpolyglutamate synthetase activity compared to an otherwise identical microorganism (reference microorganism); b) has been (further) modified to express a heterologous polypeptide having only dihydrofolate synthase activity; c) has been (further) modified to have an increased expression level of at least one enzyme (such as at least two, at least three, at least four, at least five, at least six, at least seven or at least eight) enzymes involved in the biosynthesis of a 5-methylfolate compared to an otherwise identical microorganism (reference microorganism); and/or d) has been (further) modified to have a decreased expression and/or activity of a polypeptide having 5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activity compared to an otherwise identical microorganism (ref