The present disclosure features useful compositions and methods to treat disorders for which deamination of an adenosine in an mRNA produces a therapeutic result,

Disclosed herein include guide RNA (gRNA), such as single gRNA (sgRNA), and compositions thereof, comprising 2′-O-methyldithiomethyl modified sugar moieties which can be reduced to 2′-O-methanethiol groups in the reducing environment of cells and then converted (e.g., spontaneously converted) to 2′-OH. The resultant gRNA can bind to and direct the activity of an RNA-guided endonuclease (e.g., Cas9).

The present invention relates to the field of neurological diseases, particularly to neurodegenerative diseases caused by dipeptide repeat toxicity. The invention provides genetic and chemical inhibitors of the protein kinase NEK6 to treat amyotrophic lateral sclerosis and frontotemporal dementia.

The present embodiments provide methods, compounds, and compositions useful for inhibiting or reducing SARS-CoV-2 replication, infectivity, viral titer, or viral load, which can be useful for preventing or treating COVID-19 in an individual.

The present embodiments provide methods, compounds, and compositions useful for inhibiting or reducing SARS-CoV-2 replication, infectivity, viral titer, or viral load, which can be useful for preventing or treating COVID-19 in an individual.

The present invention is directed to provide novel RNA molecules, chimeric NA molecules, double-stranded RNA molecules, and double-stranded chimeric NA molecules. Specifically, an embodiment of the present invention is an RNA molecule for RNA interference to target a mutant allele with a point mutation, in which (1) the molecule has a nucleotide sequence complementary to a nucleotide sequence of a coding region of the mutant allele; and (2) when counted from the base at the 5′-end in a nucleotide sequence complementary to a nucleotide sequence of the mutant allele, (2-1) a base at position 5 or 6 is mismatched to a base in the mutant allele; (2-2) a position 10 or 11 corresponds to the position of the point mutation; and (2-3) a group at the 2′-position of a pentose at positions 6-8 or positions 7 and 8 is modified with, e.g., OCH.sub.3. In this RNA molecule, one or more ribonucleotides may be replaced by, e.g., a deoxyribonucleotide. The molecule may form a double-stranded RNA with a complementary strand.

Disclosed herein are methods and compositions for enhancing gene targeting. The method entails co-administrating to a cell a targeting molecule and a means of enhancing the function of the targeting molecule upon delivery to the cell. The means of enhancing the function of the targeting molecule including one or more of a stressor that induces cellular stress, a proton sponge molecule, and an endosome or lysosome inhibitor. Compositions disclosed include a targeting molecule and one or more of a stressor that induces cellular stress, a proton sponge molecule, and an endosome or lysosome inhibitor.

The present disclosure describes compositions of matter comprising a ribonucleoprotein complex comprising a nucleic acid-guided nuclease and a guide RNA, and further comprising and a blocking nucleic acid molecule represented by Formula I, wherein Formula I in the 5′-to-3′ direction comprises: A-(B-L).sub.J-C-M-T-D; wherein A is 0-15 nucleotides in length; B is 4-12 nucleotides in length; L is 3-25 nucleotides in length; J is an integer between 1 and 10; C is 4-15 nucleotides in length; M is 1-25 nucleotides in length or is absent, wherein if M is absent then A-(B-L).sub.J-C and T-D are separate nucleic acid strands; T is 17-135 nucleotides in length and comprises at least 50% sequence complementarity to B and C; D is 0-10 nucleotides in length and comprises at least 50% sequence complementarity to A; and wherein the blocking nucleic acid molecule comprises a sequence complementary to a gRNA.

The present invention provides methods for cancers associated with a TERT promoter mutation in a subject. In some embodiments, the methods comprise administering to the subject a therapeutically effective amount of an agent that specifically reduces or inhibits GA binding protein transcription factor beta subunit 1 long isoform (GABPBIL) expression or function.

The present disclosure relates to an anti-miRNA delivery system, and more specifically, relates to a technique of using a cancer-targeting anti-miRNA delivery system including porous silicon nanoparticles containing anti-miRNA to which a cancer cell surface protein-binding peptide is conjugated, for use in treating cancer. As a result of intensive studies in order to use and apply anti-miR-21 oligonucleotides to the treatment of ovarian cancer, the present inventors confirmed for the first time that when porous silicon nanoparticles containing an anti-miRNA-21 oligonucleotide to which a specific cancer cell surface protein-binding peptide is conjugated are applied, apoptosis is induced in an ovarian cancer cell line and cell viability is reduced, thus, an anti-miRNA delivery system, which is the aforementioned conjugate, is expected to be usefully used as a platform for treating various cancers, especially for treating ovarian cancer.