COMPOSITIONS COMPRISING THERAPEUTIC NUCLEIC ACID AND TARGETED SAPONIN FOR THE TREATMENT OF MUSCLE-WASTING DISORDERS

The invention lies in the field of treatment and prophylaxis of muscle wasting disorders, in particular the ones involving a genetic factor that can be targeted by a delivery of a therapeutic nucleic acid into the muscle cells. In line with the latter aspect, disclosed herein are pharmaceutical compositions and advantageous components thereof that substantially enhance the effective delivery and release of a therapeutic nucleic acid into the correct internal compartment of the muscle cell, such as the cytosol and/or the nucleus, in which compartment it can reach and act upon its genetic target. As disclosed herein, this substantially enhanced delivery and release is achieved by a provision of an endosomal-escape-enhancing saponin that is specifically targeted to muscle cells by covalent conjugation with a ligand of an endocytic receptor present on a muscle cell, into a pharmaceutical composition comprising a therapeutic nucleic acid. As for the first time demonstrated herein, these saponin types surprisingly retain their endosomal-escape-enhancing properties in fully differentiated muscle cells.