The disclosure provides, inter alia, hybridized nucleic acid sequences and compounds comprising Toll-like receptor 9-binding nucleic acid sequences and nucleic acid sequences comprising a microRNA passenger strand sequence hybridized to a microRNA guide strand sequence; pharmaceutical compositions comprising the hybridized nucleic acid sequences and compounds; and the use of the hybridized nucleic acid sequences, compounds, and pharmaceutical compositions to treat medical conditions, such as cancer and inflammatory diseases.

The present invention provides extrcellular vesicles, such as exosomes, engineered to be loaded with miR-345, which may be further loaded with, e.g., miR-146a and let-7b, and/or further be depleted of miR-10a and/or miR-10b. The present invention also provides an assay method, wherein the amounts of miR-345, miR146a, and let-7b in a sample of extracellular vesicles are positively associated with potency, and wherein the amount of miR-10b in a sample of extracellular vesicles is negatively associated with potency.

Recombinant adenovirus genomes that include a synthetic transcriptional circuit are described. Synthetic adenoviruses positively regulated using two-step transcriptional amplification (TSTA) are further described. Selection of the heterologous promoter is based on the desired replication characteristics of the synthetic virus. For example, the heterologous promoter can be a constitutive promoter, a tumor-specific promoter or a tissue-specific promoter.

Provided are compositions and methods for using the same. In some embodiments, the compositions include an EPELN encapsulating and/or having associated therewith an active agent and a plasma membrane derived from a tumor and/or cancer cell coating the EPELN. In some embodiments, the active agent is a therapeutic agent or an immune response modifier, and in some embodiments the plasma membrane has one or more tumor-associated and/or cancer-associated antigens. Also provided are methods for using the compositions for treating tumors and/or cancers, inducing anti-tumor and/or anti-cancer immune responses, activating antigen-presenting cells, targeting CD11c dendritic cells, and preventing or reducing metastasis.

A recombinant adeno-associated virus (rAAV) comprising an AAV capsid and a vector genome comprising a frataxin gene is provided. Also provided is a composition containing an effective amount of rAAV to ameliorate symptoms of Freidreich’s ataxia, including, e.g., reduction in progression towards neurocognitive decline and/or cardiomyopathy.

The present disclosure describes, in part, compositions and methods for the treatment of NASH and NASH-associated diseases. Compositions comprising an agent able to increases the expression, activity, or level of one more of a protective miRNA, preferably miR-375 are provided that may be used for the treatment of liver and/or liver-associated disease is treated in the subject.

Provided are compositions and methods useful in regenerating damaged tissue, especially cardiac tissue, by delivering to the site of injury an miRNA that can reduce, for example, the expression of phosphatase and tensin homolog (PTEN). The compositions and methods of the disclosure may be generally applied to deliver an miRNA to a cell or tissue such as, but not limited to, a neuron, a smooth muscle cell, or a tumor cell. The compositions comprise a transmembrane carrier peptide conjugated, optionally by a linker, to an oligonucleotide complementary to an miRNA. The carrier peptide facilitates the entry of the miRNA into cells and for delivery to a tissue of an animal or human may be mixed with an extracellular matrix-derived hydrogel carrier.

The disclosure relates to compositions, methods, and kits for using perillyl alcohol and/or an Argonaute protein (e.g., Ago-2) to deliver a polynucleotide to a cell. The disclosure also relates to compositions, methods, and kits for treating a condition by using perillyl alcohol and/or an Argonaute protein (e.g., Ago-2) to deliver a polynucleotide to a cell. The conditions may be brain vascular diseases and brain tumors.

The present disclosure is directed to methods of inducing rejuvenation in a population of adult glial progenitor cells, and methods of treating a subject having a myelin deficiency. The method of inducing rejuvenation in a population of adult glial progenitor cells, may comprise: administering, to the population of adult glial progenitor cells, one or more nucleic acid molecules encoding microRNAs, wherein administering suppresses the signal transducer and activator of transcription 3 (STAT3) signaling pathway; and/or administering microRNAs, wherein administering suppresses the E2F transcription factor 6 (E2F6) signaling pathway; and/or administering microRNAs, wherein administering suppresses the Myc-associated factor X (MAX) signaling pathway, wherein said one or more nucleic acid molecules are administered in an amount sufficient to induce rejuvenation in the population of adult glial progenitor cells.

Disclosed herein is a formulation comprising an extracellular vesicle (EV), and a therapeutic active agent induced or embedded in the EV. According to preferred embodiments of the present disclosure, the EV is isolated from umbilical cord mesenchymal stem cells, and the active agent may be a growth factor, an immune-modulating agent, a small molecule, an siRNA, cDNA or a plant ingredient; for example, curcumin. Also disclosed herein are methods for producing the present formulation, and uses of the present formulation in the treatment of various diseases.