Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits activity of a pro-atrophy gene. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

The present disclosure provides oligonucleotide compositions comprising (1) an oligonucleotide of the present disclosure, e.g., an ASO, siRNA, shRNA, DNA or RNA aptamer, gene therapy vector, miRNA, miRNA mimic, antimiR, DNA or RNA decoy, CpG oligonucleotide, or any therapeutic or diagnostic oligonucleotide known in the art, and (ii) a caprylic acid derivative, e.g., 5-CNAC. In some aspects, the oligonucleotide composition is formulated for delivery to the gastrointestinal tract. Thus, some aspects, the present disclosure provides oligonucleotide compositions for oral delivery comprising a therapeutic or diagnostic oligonucleotide (e.g., an ASO) and a caprylic acid derivative (e.g., 5-CNAC or de derivative thereof).

Described herein are methods of prolonging or reactivating organogenesis in a subject in need thereof (e.g., a subject that has impaired organ function such as a prematurely born infant). The methods comprise increasing the expression or activity of Lin28A or Lin28B proteins, inhibiting the expression or activity of let-7 family microRNAs, and/or inhibiting the expression or activity of Dis3L2 exonuclease.

The present invention relates to a cationic lipid having one or more biodegradable groups located in a lipidic moiety (e.g., a hydrophobic chain) of the cationic lipid. These cationic lipids may be incorporated into a lipid particle for delivering an active agent, such as a nucleic acid. The invention also relates to lipid particles comprising a neutral lipid, a lipid capable of reducing aggregation, a cationic lipid of the present invention, and optionally, a sterol. The lipid particle may further include a therapeutic agent such as a nucleic acid.

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Compositions and methods are provided for the inhibition, treatment and/or prevention of degenerative myelopathy (DM) or amyotrophic lateral sclerosis (ALS).

The present invention relates to an inhibitor of DJ-1 (PARK7) for use in a method of treatment or prevention of immunoaging in a subject. In particular, the present invention relates to an inhibitor of DJ-1 for use in a method of treatment or prevention of an immunoaging-related disease in a subject, for use in a method of treatment or prevention of a premature aging disease in a subject, or for use in a method of treatment or prevention of vaccination inefficiency in a subject. In particular embodiments, the subject has been selected to have or has a premature aging disease, such as progeria, or the subject is an elderly subject.

Disclosed herein are inhibitors of PPM 1 A, including PPM1A antisense oligonucleotide sequences, and methods for treating neurological diseases, such as amyotrophic lateral sclerosis and frontotemporal dementia, associated with decreased activity or expression of TBK1. Also disclosed are pharmaceutical compositions containing a PPM1A inhibitor, including a PPM1A antisense oligonucleotide, useful for treating neurological diseases and manufacture of medicaments containing a disclosed PPM1A inhibitor, for example, a PPM1A antisense oligonucleotide, to be used in treating a neurological disease

Provided are methods for prophylaxis or therapy of cancer. The methods are directed to cancers that are characterized by expression of a mutant p53. The mutant p53 may be a loss of function p53 mutant, dominant negative p53 mutant, or a gain of function p53 mutant. The method comprises delivering to cancer cells an agent that can inhibit expression of prolidase (PEPD) or disrupts the association of mutant p53 with PEPD.

The present invention relates to compositions, methods, uses and kits for the treatment of renal cystogenesis. In particular, the compositions, methods, uses and kits are particularly useful, but not limited to, the treatment or prevention of Polycystic Kidney Disease. In one aspect, the prevent invention provides a method of minimising or delaying renal cystogenesis in a subject in need thereof, the method comprising inhibiting AKT in the subject, or reducing the level of Aurora kinase in the subject, thereby minimising or delaying renal cystogenesis.

The present disclosure relates to compositions, such as siRNA molecules and FN3 domains conjugated to the same, as well as methods of making and using the molecules.