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##

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##

Combination therapy methods, compositions and kits Invention relates to combinations comprising: a) a compound of formula (I)

##STR00001##

or a pharmaceutically or veterinary acceptable salt thereof, wherein:
R.sub.1 R.sub.2 and R.sub.3 have particular meaning; and (b) one or more drugs selected from the group consisting of i) a compound of formula (IV), or a pharmaceutically or veterinary acceptable salt thereof,

##STR00002##

wherein R.sub.5 and R.sub.6 have particular meaning, ii) a sphingosine-1-phosphate receptor inhibitor (S1PR modulator), and iii) a Signal transducer and activator of transcription 3 (STAT3) inhibitor. Particular combinations and single pharmaceutical compositions and kits of parts are disclosed. These combinations, single pharmaceutical compositions and kits of parts are for use in the treatment and/or prevention of an inflammatory neurological disease or condition which can result in the destruction or degeneration of axons or myelin in a subject in need thereof

Combination therapy methods, compositions and kits Invention relates to combinations comprising: a) a compound of formula (I)

##STR00001##

or a pharmaceutically or veterinary acceptable salt thereof, wherein:
R.sub.1 R.sub.2 and R.sub.3 have particular meaning; and (b) one or more drugs selected from the group consisting of i) a compound of formula (IV), or a pharmaceutically or veterinary acceptable salt thereof,

##STR00002##

wherein R.sub.5 and R.sub.6 have particular meaning, ii) a sphingosine-1-phosphate receptor inhibitor (S1PR modulator), and iii) a Signal transducer and activator of transcription 3 (STAT3) inhibitor. Particular combinations and single pharmaceutical compositions and kits of parts are disclosed. These combinations, single pharmaceutical compositions and kits of parts are for use in the treatment and/or prevention of an inflammatory neurological disease or condition which can result in the destruction or degeneration of axons or myelin in a subject in need thereof

Provided are therapies, including standalone and combination therapies, for treating neuropilin-2 (NRP2)-associated diseases and conditions, which include the use of at least one histidyl-tRNA synthetase (HRS) polypeptide.

Provided are therapies, including standalone and combination therapies, for treating neuropilin-2 (NRP2)-associated diseases and conditions, which include the use of at least one histidyl-tRNA synthetase (HRS) polypeptide.

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.

Provided herein are methods for managing host immune responses to improve therapeutic outcomes in adeno-associated virus (AAV)-mediated gene therapy. Such methods may include administering a recombinant adeno-associated vims (rAAV) to a subject following administration of a CD 19 inhibitor, e.g., an anti-CD 19 antibody. The methods described herein can facilitate improved transgene expression, help overcome pre-existing NAbs, and/or permit redosing with the same or substantially similar rAAV or transgene.

Provided herein are methods for managing host immune responses to improve therapeutic outcomes in adeno-associated virus (AAV)-mediated gene therapy. Such methods may include administering a recombinant adeno-associated vims (rAAV) to a subject following administration of a CD 19 inhibitor, e.g., an anti-CD 19 antibody. The methods described herein can facilitate improved transgene expression, help overcome pre-existing NAbs, and/or permit redosing with the same or substantially similar rAAV or transgene.