Abstract: The present disclosure includes cationic carrier units comprising (i) a water-soluble polymer, (ii) a positively charged carrier, (iii) a hydrophobic moiety, and (iv) a crosslinking moiety, wherein when the cationic carrier unit is mixed with an anionic payload (e.g., an antisense oligonucleotide) that electrostatically interacts with the cationic carrier unit, the resulting composition self-organizes into a micelle encapsulating the anionic payload in its core. The cationic carrier units can also comprise a tissue specific targeting moiety, which would be displayed on the surface of the micelle. The disclosure also includes micelles comprising the cationic carrier units of the disclosure, methods of manufacture of cationic carrier units and micelles, pharmaceutical compositions comprising the micelles, and also methods of treating diseases or conditions comprising administering the micelles to a subject in need thereof.

Abstract: The present disclosure includes cationic carrier units comprising (i) a water soluble polymer, (ii) a positively charged carrier, (iii) a hydrophobic moiety, and (iv) a crosslinking moeity, wherein when the cationic carrier unit is mixed with an anionic payload (e.g., an RNA and/or DNA) that electrostatically interacts with the cationic carrier unit, the resulting composition self-organizes into a micelle encapsulating the anionic payload in its core. The cationic carrier units can also comprise a tissue specific targeting moiety, which would be displayed on the surface of the micelle. The disclosure also includes micelles comprising the cationic carrier units of the disclosure, methods of manufacture of cationic carrier units and micelles, pharmaceutical compositions comprising the micelles, and also methods of treating diseases or conditions comprising administering the micelles to a subject in need thereof.

Abstract: The present disclosure includes cationic carrier units comprising (i) a water soluble polymer, (ii) a positively charged carrier, and (iii) an adjuvant moiety, wherein when the cationic carrier unit is mixed with an anionic payload (e.g., an antisense oligonucleotide) that electrostatically interacts with the cationic carrier unit, the resulting composition self-organizes into a micelle encapsulating the anionic payload in its core. The cationic carrier units can also comprise a tissue specific targeting moiety, which would be displayed on the surface of the micelle. The disclosure also includes micelles comprising the cationic carrier units of the disclosure, methods of manufacture of cationic carrier units and micelles, pharmaceutical compositions comprising the micelles, and also methods of treating diseases or conditions comprising administering the micelles to a subject in need thereof.

Abstract: The present disclosure includes the use of a miRNA inhibitor for treating a symptom or condition of Huntington’s disease. The miRNA inhibitor useful for the present disclosure can inhibit miR-485 expression and/or activity, which in turn can modulate the level of proteins or gene expression related to Huntington’s disease.

Abstract: The present disclosure includes the use of a miRNA inhibitor for treating amyotrophic lateral sclerosis (ALS) associated with a decreased level of SIRT1 protein or SIRT1 gene expression, PGC-1? protein and/or PGC-1? gene expression, CD36 protein and/or CD36 gene expression, NRG1 protein and/or NRG1 gene expression, STMN2 protein and/or STMN2 gene expression, and/or NRXN1 protein and/or NRXN1 gene expression.

Abstract: The present disclosure includes the use of a miRNA inhibitor for treating a disease or condition associated with a decreased level of SIRT1, PGC-1?, CD36, LRRK2, NRG1, STMN2, VLDLR, NRXN1, GRIA4, NXPH1, PSD-95, and/or synaptophysin protein or SIRT1, PGC-1?, CD36, LRRK2, NRG1, STMN2, VLDLR, NRXN1, GRIA4, NXPH1, PSD-95, and/or synaptophysin gene expression. In some aspects, the miRNA inhibitor can be used to treat a disease or condition associated with an increased level of caspase-3 protein or gene expression. The miRNA inhibitor useful for the present disclosure can inhibit miR-485 expression and/or activity, which in turn can increase the level of SIRT1, PGC-1?, CD36, LRRK2, NRG1, STMN2, VLDLR, NRXN1, GRIA4, NXPH1, PSD-95, and/or synaptophysin protein or gene expression; and/or can decrease the level of caspase 3 protein or gene expression.

Abstract: The present disclosure relates to the use of SIRT1 expression to identify a subject that is conducive to treatment with a miR-485 inhibitor. In some aspects, the subject suffers from a disease or disorder associated with reduced SIRT1 expression. In some aspects, the SIRT1 expression is measured in the serum of the subject.

Abstract: The present disclosure relates to the use of PGC-1? expression to identify a subject that is conducive to treatment with a ma-485 inhibitor. In some aspects, the subject suffers from a disease or disorder associated with reduced PGC-1? expression. In some aspects, the PGC-1? expression is measured in the serum of the subject.

Abstract: The present disclosure includes the use of a miRNA inhibitor for treating a tauopathy associated with a decreased level of SIRT1 protein or SIRT1 gene expression, PGC-1? protein and/or PGC-? gene expression, and/or CD36 and/or CD36 gene expression.

Abstract: The present disclosure includes cationic carrier units comprising (i) a water soluble polymer, (ii) a positively charged carrier, and (iii) an adjuvant moiety, wherein when the cationic carrier unit is mixed with an anionic payload (e.g., an antisense oligonucleotide) that electrostatically interacts with the cationic carrier unit, the resulting composition self-organizes into a micelle encapsulating the anionic payload in its core. The cationic carrier units can also comprise a tissue specific targeting moiety, which would be displayed on the surface of the micelle. The disclosure also includes micelles comprising the cationic carrier units of the disclosure, methods of manufacture of cationic carrier units and micelles, pharmaceutical compositions comprising the micelles, and also methods of treating diseases or conditions comprising administering the micelles to a subject in need thereof.

Abstract: The present disclosure includes cationic carrier units comprising (i) a water soluble polymer, (ii) a positively charged carrier, and (iii) an adjuvant moiety, wherein when the cationic carrier unit is mixed with an anionic payload (e.g., an antisense oligonucleotide) that electrostatically interacts with the cationic carrier unit, the resulting composition self-organizes into a micelle encapsulating the anionic payload in its core. The cationic carrier units can also comprise a tissue specific targeting moiety, which would be displayed on the surface of the micelle. The disclosure also includes micelles comprising the cationic carrier units of the disclosure, methods of manufacture of cationic carrier units and micelles, pharmaceutical compositions comprising the micelles, and also methods of treating diseases or conditions comprising administering the micelles to a subject in need thereof.