Aspects of the disclosure relate to complexes and other aspects relate to formulations (e.g., aqueous, lyophilized forms) comprising such complexes (e.g., wherein each complex is of the exemplary formula shown below) comprising a phosphorodiamidate morpholino oligomer (e.g., useful for targeting DMD) covalently linked to an antibody (e.g., anti-TfR1 antibody). In some embodiments, the complexes are formulated with histidine (e.g., L-histidine) and sucrose at a specified pH (e.g., about 5.0 to 7.0). Also provided are uses of these formulations for treating a subject having a mutated DMD allele associated with Duchenne Muscular Dystrophy.

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Provided herein are therapeutic oligonucleotides that comprise at least one p-ethoxy backbone linkage but no more than 80% p-ethoxy backbone linkages. Provided herein are improved delivery systems for therapeutic oligonucleotides comprising a liposome that comprises neutral phospholipids and a p-ethoxy oligonucleotide that is entrapped in the liposome.

Metal-bisphosphonate nanoparticles are disclosed. Also disclosed are pharmaceutical compositions including the metal-bisphosphonate nanoparticles, methods of preparing the metal-bisphosphonate nanoparticles and materials comprising the nanoparticles, and methods of using the compositions to treat cancer or bone-related disorders (e.g., bone-resorption-related diseases, osteoporosis, Paget's disease, and bone metastases) and as imaging agents.

The present disclosure relates to a pharmaceutical composition for treating, preventing and/or ameliorating spinal muscular atrophy (SMA) and a method of administration thereof. A pharmaceutical composition for treating, preventing and/or ameliorating SMA according to an embodiment of the present disclosure may comprise a SMN protein, which is the cause of the onset of SMA. The pharmaceutical composition may be administered directly to a subject suffering from SMA via intracerebroventricular, intrathecal or intra-cisterna magna administration, thereby treating or preventing SMA or ameliorating symptoms of SMA. The pharmaceutical composition for treating, preventing or ameliorating SMA according to one embodiment of the present disclosure is safe, cost-effective and/or accessible compared to other previously approved drugs and can achieve substantially equivalent therapeutic effects.

A composition of matter comprising a synthetic miR-135 molecule comprising a nucleic acid sequence of a miR-135b as set forth in SEQ ID NO: 37, and a complementary strand as set forth in SEQ ID NO: 40 is disclosed. A conjugate comprising a composition of matter comprising a synthetic miR-135 molecule and a cell-targeting moiety is also disclosed.

In various embodiments deformable nano-scale vehicles (DNV) are provided that are useful for the delivery of therapeutic agents. In certain embodiments the DNVs are capable of transdermal delivery and can additionally cross the blood-brain barrier.

Disclosed are peptides capable of enzymatically-induced self-assembly to which is conjugated a redox modulator. These peptides are enzymatically responsive hydrogelators, and they can be used to form pericellular hydrogels/nanofibrils upon exposure to target cells that secrete or express a surface bound ectoenzyme having hydrolase activity suitable to induce peptide gelation. These materials, and compositions containing the same, can be used for inhibiting cancer cell migration, inhibiting cancer cell survival, and/or inhibiting cancer cell growth.

Nanoparticles include a core, a hydrophilic layer around the core, and one or more mitochondrial targeting moieties, and may optionally include one or more contrast agents or one or more therapeutic agents. For effective mitochondrial targeting the nanoparticles have a diameter of about 200 nm or less or have a zeta potential of about 0 mV or more.

Provided are formulations, methods, and devices for providing a hydrogel. The formulations and resulting hydrogels may be used for treating various disorders, including ocular disorders. In certain embodiments, the hydrogel is formed from formulations comprising (a) a nucleo-functional polymer that is a biocompatible polyalkylene polymer substituted by (i) a plurality of OH groups, (ii) a plurality of thio-functional groups R.sup.1SH wherein R.sup.1 is an ester-containing linker, and (iii) optionally one or more OC(O)(C.sub.1-C.sub.6 alkyl) groups, such as a thiolated poly(vinyl alcohol) polymer; (b) an electro-functional polymer that is a biocompatible polymer containing at least one thiol-reactive group, such as a poly(ethylene glycol) polymer containing alpha-beta unsaturated ester groups; and (c) one or more pharmaceutically active agents. In certain embodiments, the hydrogel is formed at a targeted sited using methods and/or devices for focal administration of the formulations and/or hydrogels described herein.

Phosphonate linkers and their use for delivering compounds with passive cell permeability into a cell wherein the phosphonate group facilitates cellular retention of the compound are described.