The present disclosure provides compositions and methods that inhibit the activity of microRNAs, for example miR-22.

The present disclosure, at least in part, relates to a miRNA based logic gate that comprises an engineered RNA carrier that comprises an nuclear export signal, a target site for a first miRNA and a pre-miRNA sequence for a second miRNA. Also provided by the disclosure are recombinant viruses (e.g., recombinant adeno-associated viruses (rAAV)) for delivery of the miRNA based logic gates.

Provided is a composition for treating tumors in a subject comprising a therapeutically effective amount of an exosome carrying CTLA4-targeting miRNA and a therapeutically effective amount of an oncolytic herpes simplex virus expressing an immunostimulatory agent or both an immunostimulatory agent and an anti-PD-1 antibody. Wherein an exo-motif operably links to the seed sequence of the CTLA4-targeting miRNA to enhance the packaging of the CTLA4-targeting miRNA into the exosome.

The present invention relates to a conditionally switchable nanostructure configured to assume a first configuration and a second configuration, wherein the nanostructure comprises a binding site that is configured to bind to a binding target, and wherein the accessibility of the binding site for the binding target in the second configuration is different to the accessibility of the binding site for the binding target in the first configuration. Further, the nanostructure is configured to assume the first configuration when none of the coupling sites of the coupling site set is coupled to its respective coupling target and to assume the second configuration when each coupling site of a subset of the coupling site set is coupled to its respective coupling target, wherein the subset comprises at least one coupling site. Additionally, the present technology also relates to a system comprising the nanostructure as well as a method utilizing the nanostructure or the system. Finally, the nanostructure may be comprised in a substance or composition for use as a medicament.

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 disclosure features useful compositions and methods to treat disorders for which deamination of an adenosine in an mRNA produces a therapeutic result, e.g., in a subject in need thereof.

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.

The present invention provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell.

The present disclosure, at least in part, relates to a miRNA based logic gate that comprises an engineered RNA carrier that comprises an nuclear export signal, a target site for a first miRNA and a pre-miRNA sequence for a second miRNA. Also provided by the disclosure are recombinant viruses (e.g., recombinant adeno-associated viruses (rAAV)) for delivery of the miRNA based logic gates.

The present invention refers to a modified D-amino acid oxidase (DAAO). In particular, the modified DAAO of the present invention has the activity of catalyzing the oxidation of D-glufosinate into PPO. Further, the modified DAAO of the present invention has increased activity of catalyzing the oxidation of D-glufosinate into PPO and/or increased stability as compared to SEQ ID NO: 4. The present invention also refers to the polynucleotide encoding the modified DAAO of the present invention, the vector and host cell expressing the modified DAAO of the present invention, and the method of producing L-glufosinate with the modified DAAO and host cell of the present invention.