The present invention provides, among other things, methods of delivering mRNA in vivo, including administering to a subject in need of delivery a composition comprising an mRNA encoding a protein, encapsulated within a liposome such that the administering of the composition results in the expression of the protein encoded by the mRNA in vivo, wherein the liposome comprises a cationic lipid of formula I-c: ##STR00001##
or a pharmaceutically acceptable salt thereof.

The present invention provides, among other things, methods of delivering mRNA in vivo, including administering to a subject in need of delivery a composition comprising an mRNA encoding a protein, encapsulated within a liposome such that the administering of the composition results in the expression of the protein encoded by the mRNA in vivo, wherein the liposome comprises a cationic lipid of formula I-c: ##STR00001##
or a pharmaceutically acceptable salt thereof.

The present invention relates to extracellular vesicle (EV)-mediated delivery of protein-based therapeutics. More specifically, the invention relates to delivery of complex polypeptide-based agents which typically bind to target proteins extracellularly, intracellularly, or in the cell membrane.

Provided are therapies, including combination therapies, for the treatment of lung inflammation, including interstitial lung diseases (ILDs), which include the use of at least one histidyl-tRNA synthetase (HRS) polypeptide or an expressible polynucleotide that encodes the HRS polypeptide, alone or in combination with at least one immunomodulatory agent.

Provided are therapies, including combination therapies, for the treatment of lung inflammation, including interstitial lung diseases (ILDs), which include the use of at least one histidyl-tRNA synthetase (HRS) polypeptide or an expressible polynucleotide that encodes the HRS polypeptide, alone or in combination with at least one immunomodulatory agent.

Disclosed herein are methods and compositions for the treatment and/or prevention of diseases or conditions comprising administration of a therapeutic biological molecule, and/or naturally or artificially occurring derivatives, analogues, or pharmaceutically acceptable salts thereof, alone or in combination with one or more active agents (e.g., an aromatic-cationic peptide). The present technology provides compositions related to aromatic-cationic peptides linked to a therapeutic biological molecule and uses of the same. In some embodiments, the aromatic-cationic peptide comprises 2,6-dimethyl-Tyr-D-Arg-Phe-Lys-NH.sub.2, Phe-D-Arg-Phe-Lys-NH.sub.2, or D-Arg-2,6-Dmt-Lys-Phe-NH.sub.2.

Disclosed herein are methods and compositions for the treatment and/or prevention of diseases or conditions comprising administration of a therapeutic biological molecule, and/or naturally or artificially occurring derivatives, analogues, or pharmaceutically acceptable salts thereof, alone or in combination with one or more active agents (e.g., an aromatic-cationic peptide). The present technology provides compositions related to aromatic-cationic peptides linked to a therapeutic biological molecule and uses of the same. In some embodiments, the aromatic-cationic peptide comprises 2,6-dimethyl-Tyr-D-Arg-Phe-Lys-NH.sub.2, Phe-D-Arg-Phe-Lys-NH.sub.2, or D-Arg-2,6-Dmt-Lys-Phe-NH.sub.2.

Provided are fusion target-binding proteins comprising a target binding moiety, an intracellular signalling region and a domain that promotes synthesis of arginine or an arginine precursor. The domain may be an enzyme domain such as an argininosuccinate synthase (ASS-1) enzyme domain, or an ornithine transcarbamylase (OTC) enzyme domain. Also provided are cells comprising such a fusion target-binding protein (for example cells that express the fusion target-binding protein), and nucleic acids encoding such fusion target-binding proteins. The invention also provides fusion target-binding proteins comprising a target binding moiety, an intracellular signalling region and a domain that promotes synthesis of tryptophan or a tryptophan precursor. Pharmaceutical compositions, medical uses, and methods of treatment, all using the fusion target-binding proteins, cells, or nucleic acids are disclosed. The proteins, cells, nucleic acids and pharmaceutical compositions may be used in the prevention and/or treatment of cancer, such as neuroblastoma or acute myeloid leukaemia.

Provided are fusion target-binding proteins comprising a target binding moiety, an intracellular signalling region and a domain that promotes synthesis of arginine or an arginine precursor. The domain may be an enzyme domain such as an argininosuccinate synthase (ASS-1) enzyme domain, or an ornithine transcarbamylase (OTC) enzyme domain. Also provided are cells comprising such a fusion target-binding protein (for example cells that express the fusion target-binding protein), and nucleic acids encoding such fusion target-binding proteins. The invention also provides fusion target-binding proteins comprising a target binding moiety, an intracellular signalling region and a domain that promotes synthesis of tryptophan or a tryptophan precursor. Pharmaceutical compositions, medical uses, and methods of treatment, all using the fusion target-binding proteins, cells, or nucleic acids are disclosed. The proteins, cells, nucleic acids and pharmaceutical compositions may be used in the prevention and/or treatment of cancer, such as neuroblastoma or acute myeloid leukaemia.

Disclosed are polymers comprising the moiety A, which is a moiety of formula I: and pharmaceutically acceptable salts thereof, wherein R, R.sup.1, R.sup.2, L, n1 and n2 are as defined herein. These polymers are useful for delivering nucleic acids to subject. These polymers and pharmaceutically acceptable compositions comprising such polymers and nucleic acids can be useful for treating various diseases, disorders and conditions.

##STR00001##