Abstract: A method for scarless genome editing is disclosed. In particular, the method provides scarless genome modification by using homology directed repair (HDR) steps to genetically modify cells and remove unwanted sequences. This method can be used for genome editing, including introducing mutations, deletions, or insertions at any position in the genome without leaving silent mutations, selection marker sequences, or other additional undesired sequences in the genome.

Abstract: The present disclosure provides a modified human OTC protein having improved properties for the treatment of OTC deficiency in a patient. Preferably, the protein of the disclosure is produced from a codon optimized mRNA suitable for administration to a patient suffering from OTC deficiency wherein upon administration of the mRNA to the patient, the protein of the disclosure is expressed in the patient in therapeutically effective amounts to treat OTC deficiency. The present disclosure also provides codon optimized mRNA sequences encoding wild type human OTC comprising a 5? UTR derived from a gene expressed by Arabidopsis thaliana for use in treating OTC deficiency in a patient.

Abstract: Provided herein are recombinant circular RNA (circRNA) molecules comprising an internal ribosome entry site (IRES) operably linked to a protein-coding nucleic acid sequence. The IRES includes at least one RNA secondary structure element; and a sequence region that is complementary to an 18S ribosomal RNA (rRNA). Methods of producing a protein in a cell using the recombinant circRNA molecules are also provided.

Abstract: The present invention relates to a non-thermal atmospheric-pressure plasma keloid treatment device and a use thereof. The non-thermal atmospheric-pressure plasma keloid treatment device according to the present invention has effects of inhibiting collagen deposition in keloid fibroblasts and mobility thereof, and thus, is expected to be greatly useful for preventing and treating keloids.

Abstract: The present disclosure also relates to compositions and methods relating to reducing the potency of arthropods using double-stranded RNA and agents to control pests of bees and beehives.

Abstract: The present invention discloses a method for establishing a colorectal cancer p73 reporter gene cell line, specifically including: first designing a site-specific sgRNA sequence of a p73 gene and cloning same into a plasmid PX459; integrating a homologous recombination sequence of the p73 gene and a green fluorescent protein DNA fragment (EGFP), and transforming the plasmid and the integrated fragment together into a colorectal cancer cell line HCT116 by electroporation; performing signal cell screening through a flow cytometer to obtain EGFP-expressing cells, and amplifying a monoclonal cell line; and identifying a positive p73 reporter gene cell line through PCR identification and Western blot, among screened EGFP-expressing cell lines. The colorectal cancer cell line p73 gene and the EGFP are co-expressed, and the expression level of the EGFP is highly consistent with that of the p73 gene.

Abstract: The present invention relates to a composition or cell therapeutic agent for preventing or treating liver fibrosis, containing an exosome or exosome-derived ribonucleic acid. The exosome or ribonucleic acid derived therefrom, of the present invention, has effects of inhibiting activities of hepatic stellate cells and Kupffer cells and reducing the expression of ?-SMA and inhibits the progression of liver fibrosis by inhibiting the deposition of collagen, thereby being effectively usable as a cell therapeutic agent for the prevention or treatment of liver fibrosis.

Abstract: The present invention provides methods and composition of a novel mechanism using the bioenergetic Cyclocreatine Phosphate as a potent cardioprotective drug by preserving cellular energy source, preventing ischemic injury, rejuvenating organ function, thus, maintaining normal physical activity. Cyclocreatine Phosphate can be used as a new therapeutic approach to prevent disease development and progression, and to treat ischemia-induced diseases in ischemic heart disease patients, including: coronary artery disease, unstable angina, acute myocardial infarction, heart failure, atrial fibrillation, and Takotsubo cardiomyopathy, as well as provides cardioprotection during cardiac procedures and surgeries. The invention further provides methods and composition to prevent and treat aging-related neurodegenerative diseases where hypoxia/ischemia play a key role in the development and progression of the disease.

Abstract: The present disclosure provides compositions which shown preferential targeting or delivery of a nucleic acid composition to a particular organ. In some embodiments, the composition comprises a steroid or sterol, an ionizable cationic lipid, a phospholipid, a PEG lipid, and a permanently cationic lipid which may be used to deliver a nucleic acid.

Abstract: The present disclosure provides compositions which shown preferential targeting or delivery of a nucleic acid composition to a particular organ. In some embodiments, the composition comprises a steroid or sterol, an ionizable cationic lipid, a phospholipid, a PEG lipid, and a permanently cationic lipid which may be used to deliver a nucleic acid.

Abstract: The present invention provides pharmaceutical compositions comprising membrane vesicles, including extracellular vesicles including those referred to as exosomes, loaded with an exogenous Phosphatase and tensin homolog (PTEN) inhibitor. Methods of treating neurological diseases, disorders or conditions using the extracellular vesicles are provided. Isolated extracellular vesicles loaded with an exogenous Phosphatase and tensin homolog (PTEN) inhibitor are provided as well.

Abstract: A method comprising administering, to a subject in need thereof, an effective amount of a nucleotide effective to disrupt one or more pathways leading to sepsis. The nucleotide may be a nitric oxide disruptor effective to decrease the expression of inducible nitric oxide synthase. The nitric oxide disrupter may comprise a polynucleotide strand exhibiting at least 70% sequence identity to one of Sequence ID No. 1 through Sequence ID No. 47. Additionally or alternatively, the nucleotide may be an ? disintegrin and metalloproteinase (ADAM) enzyme inhibitor effective to decrease the expression of ADAM enzyme. The ADAM enzyme inhibitor may comprise a polynucleotide strand exhibiting at least 70% sequence identity to one of Sequence ID No. 48 through Sequence ID No. 56.

Abstract: The invention provides compositions and methods for reducing expression of a target gene in a cell, involving contacting a cell with an isolated double stranded nucleic acid (dsNA) in an amount effective to reduce expression of a target gene in a cell. The dsNAs of the invention possess a single stranded extension (in most embodiments, the single stranded extension comprises at least one modified nucleotide and/or phosphate back bone modification). Such single stranded extended Dicer-substrate siRNAs (DsiRNAs) were demonstrated to be effective RNA inhibitory agents compared to corresponding double stranded DsiRNAs.

Abstract: The present invention relates to a nucleic acid molecule simultaneously inhibiting the expression of mTOR gene and STAT3 gene, and an anticancer pharmaceutical composition comprising the same. More specifically, base-paired siRNA or shRNA of the present invention, designed to simultaneously inhibit the expression of cancer-related mTOR gene and STAT3 gene in order to surmount the problem that siRNA or shRNA does not achieve high therapeutic effects due to the target specificity thereof, has the effect of promoting the death of cancer cells. In addition, the nucleic acid has the effect of synergistically enhancing the apoptosis of cancer cells when used in combination with an anticancer agent, finding useful applications as an anticancer composition or anticancer aid against various carcinomas.

Abstract: The present embodiments provide methods, compounds, and compositions useful for inhibiting PCSK9 expression, which may be useful for treating, preventing, or ameliorating a disease associated with PCSK9.

Abstract: Among other things, the present disclosure relates to designed oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide altered splicing of a transcript. In some embodiments, provided oligonucleotide compositions have low toxicity. In some embodiments, provided oligonucleotide compositions provide improved protein binding profiles. In some embodiments, provided oligonucleotide compositions have improved delivery. In some embodiments, provided oligonucleotide compositions have improved uptake. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions.

Abstract: Disclosed herein are antisense compounds and methods for decreasing apo(a) to treat, prevent, or ameliorate diseases, disorders or conditions related to apo(a) or Lp(a). Certain diseases, disorders or conditions related to apo(a) or Lp(a) include inflammatory, cardiovascular and/or metabolic diseases, disorders or conditions. The antisense compounds disclosed herein can be used to treat such diseases, disorders or conditions in an individual in need thereof.

Abstract: Methods of reducing levels of virus molecules and/or treating viral infections include contacting cells with an oligonucleotide inhibitor that targets a cellular host factor that is a target RNA or target protein involved in viral replication. A pharmaceutical composition can include such an oligonucleotide inhibitor in an amount effective for treating an infection, such as a hepatitis B infection or a respiratory virus infection, such as a coronavirus infection.

Abstract: Genomic safe harbors (GSH) for genetic therapies in human stem cells and engineered nanoparticles to provide targeted genetic therapies are described. The GSH and/or associated nanoparticles can be used to safely and efficiently treat a variety of genetic, infectious, and malignant diseases.

Abstract: Shortened telomeres are diagnostic of genetic predisposition to cardiomyopathies, e.g. those related to defects in structural proteins expressed in cardiomyocytes.