Abstract: The invention is directed to compositions and methods for increasing the pH of a melanosome in a melanocyte, darkening skin or hair pigmentation, or treating a disease associated with decreased melanin comprising administering a soluble adenylyl cyclase (sAC) inhibitor and/or an exchange protein activated by cyclic AMP (EPAC) inhibitor to the melanocyte. The invention also provides compositions and methods for decreasing the pH of a melanosome in a melanocyte, lightening skin or hair pigmentation, or treating a disease associated with increased melanin comprising administering a sAC activator and/or an EPAC activator to the melanocyte.

Abstract: The present invention relates to a novel approach for treating cancer, which is based on targeting PD-L1 mRNA. The invention is directed to oligonucleotides comprising 10 to 20 modified or unmodified nucleotides complementary to specifically selected regions of the PD-L1.

Abstract: A single nucleotide polymorphism (SNP) that results in development of a Type VI collagen, alpha 1 chain-related disorder, and the use of the SNP to identify individuals at risk for developing COL6-related disorders (COL6-RD). Also provided are antisense oligomers for treating individuals at risk for developing COL6-RD, as well as methods for screening compounds for their potential as therapeutic agents.

Abstract: Antisense oligomer conjugates complementary to a selected target site in the human dystrophin gene to induce exon 51 skipping are described.

Abstract: Provided is a method for high-efficiently reading through a nonsense mutation site in a pathogenic gene in a monogenic hereditary disease and restoring the normal structure and function of a mutant protein, by using a genetic code expanded non-natural amino acid system. By modifying a tRNA of Methanosarcina barkeri (tRNAPyl), an all-new UAA and UGA encoded non-natural amino acid system that has high read-through efficiency is obtained, and the range of using the orthogonal pair of tRNAPyl and pyrrolysyl-tRNA synthetase (PylRS) is expanded. A plasmid mimicking the endogenous premature termination codon is constructed, so as to evaluate the efficiency of reading through the endogenous premature termination codon. Also provided is a system mainly comprising pathogenic genes of monogenic hereditary diseases and tumor inhibitory genes in tumor cells.

Abstract: A lentiviral vector system for expressing a lentiviral particle is disclosed. The lentiviral vector system includes a therapeutic vector, an envelope plasmid, and at least one helper plasmid. The lentiviral vector system can produce a lentiviral particle for inhibiting PARP expression in neuron cells of a subject afflicted with Parkinson's disease.

Abstract: The present disclosure provides synthetic modular polypeptide libraries and nucleic acids encoding such synthetic modular polypeptide libraries. Also provided are methods of making synthetic modular polypeptide libraries and nucleic acids encoding synthetic modular polypeptide libraries. Methods of screening a synthetic modular polypeptide library to identify a selected phenotype associated with a member of a synthetic modular polypeptide library are also provided where such methods find use in both in vitro and in vivo assays.

Abstract: This invention provides compositions, compounds, and uses thereof, wherein said compounds comprise a single strand oligonucleotide that may form a short oligonucleotide hairpin or stem loop molecule with self complementary base pairing of less than 12 base pairs that bind to RIG-I and activate the RIG-I pathway.

Abstract: Among the various aspects of the present disclosure is the provision of methods and compositions for improving exercise endurance, performance, or tolerance using an S1P inhibiting agent.

Abstract: The present invention relates to pharmaceutical compositions for preventing or treating pulmonary metastasis of cancer. More specifically, the present invention relates to compositions that enhance anti-cancer immunity of the lung rather than induce death of advanced cancer, thus being effective in inhibiting, preventing or treating pulmonary metastasis of cancer.

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: The present invention relates to a method for predicting susceptibility to sorafenib treatment by using an SULF2 gene, and a composition for treatment of sorafenib-resistant cancer using the SULF2 expression inhibition. The method for predicting susceptibility to sorafenib treatment by using the SULF2 gene according to the present invention can enable achievement of an optimal therapeutic effect by administering a drug suitable for cancer patients, and the composition for treatment of sorafenib-resistant cancer using the SULF2 inhibition has a very excellent anticancer treatment effect.

Abstract: Enhanced, specific nucleic acid targeting complexes comprising endo and exonuclease activity, and related methods that allow both targeted degradation of specific and/or non-specific nucleic acids in vivo and specific temporal regulation of nuclease activity to prevent off-target activity are disclosed herein. Through practice of the disclosure, nucleic acids, and cells harboring them, such as cancer cells or pathogens, are selectively degraded in vivo.

Abstract: The disclosure relates to nucleic acids that contain modifications at the 5?-end, 3?-end or 5?-end and 3?-ends, and compounds that can be used to make the modified nucleic acids are disclosed. The modified nucleic acids have improved expression, lower immunogenicity and improved stability compared to unmodified nucleic acids.

Abstract: The present invention provides a double-stranded nucleic acid consisting of a sense-strand nucleic acid and an antisense-strand nucleic acid and comprising a double-strand region having at least 11 base pairs, for suppressing expression of APCS gene, in which an oligonucleotide chain having a chain length of at least 17 nucleotides and at most 30 nucleotides in the antisense-strand nucleic acid is complementary to a target APCS mRNA sequence comprising a base sequence set forth in any one of SEQ ID NOS: 1288 to 1930.

Abstract: Activating transcription factor 6 (ATF6) is involved in cystic fibrosis transmembrane conductance regulator (CFTR) repression and understanding this inhibitory mechanism is of great interest to develop a therapeutic approach based on UPR regulation. Using site-1 protease (S1P) inhibitor (e.g. PF-429242) the inventors showed that both membrane localization and function of F508del-CFTR are partially restored. Accordingly, the present invention relates to a method of treating a disease associated with reduced CFTR function in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a S1P inhibitor.

Abstract: Based at least in part on an understanding of the mechanisms by which small RNAs (e.g., naturally-occurring miRNAs) mediate RNA silencing in plants, rules have been established for determining, for example, the degree of complementarity required between an RNAi-mediating agent and its target, i.e., whether mismatches are tolerated, the number of mismatches tolerated, the effect of the position of the mismatches, etc. Such rules are useful, in particular, in the design of improved RNAi-mediating agents which allow for more exact control of the efficacy of RNA silencing.

Abstract: Described herein are compositions and methods for treating Alzheimer's disease or dementia. The compositions include mammalian suppressor of taupathy 2 inhibitors (MSUT2). The MSUT2 inhibitors can be small interfering RNAs, guide RNAs, or small molecules. The methods include reducing accumulation of phosphorylated and aggregated human tau.

Abstract: The present disclosure provides compositions and methods for treating a disorder associated with mutations in the CEP290 gene. The disclosure includes synthetic polynucleotides for skipping a reading-frame of a CEP290 pre-RNA, yielding a CEP290 translated product that lacks one or more exons. The disclosure also provides methods of treating patients with the synthetic polynucleotides disclosed herein.

Abstract: The present invention relates to compositions and methods for the treatment of myotonic dystrophy.