A polyacrylamide-based copolymer reduces or prevents aggregation of biologic molecules including proteins, peptides, and nucleic acids, and lipid-based vehicles such as liposomes, lipid nanoparticles, polymerosomes, and micelles, in aqueous formulations at hydrophobic interfaces, thereby increasing the thermal stability of the molecules in the formulation. Methods and compositions comprising the copolymer and a protein or the copolymer and insulin can be used for treating conditions including diabetes.

The disclosure features novel lipids and compositions involving the same. Lipid nanoparticles (e.g., empty LNPs or loaded LNPs) include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Lipid nanoparticles (e.g., empty LNPs or loaded LNPs) further including therapeutic and/or prophylactics such as RNA are useful in the delivery of therapeutic and/or prophylactics to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.

Provided herein are lipid compounds that can be used in combination with other lipid components, such as neutral lipids, cholesterol and polymer conjugated lipids, to form lipid nanoparticles for delivery of therapeutic agents (e.g., nucleic acid molecules) for therapeutic or prophylactic purposes, including vaccination. Also provided herein are lipid nanoparticle compositions comprising said lipid compounds.

Provided herein are compositions comprising a nanoparticle and a D20 tag. The D20 tag comprises dibenzocyclooctyne (DBCO) covalently attached to a protein. Also provided are diagnostic and therapeutic methods utilizing the nanoparticle composition.

Methods of making and using nanoparticle pharmaceutical compositions comprising histidine-lysine copolymers are provided. The solutions spontaneously form nanoparticles when mixed with nucleic acids such as siRNA. Methods are provided where the pH of the nucleic acid solution is controlled prior to mixing leading to a reduction in nanoparticle diameter to a desirable range, typically 100-150 nm, and Polydispersity Index (PDI), both of which improve transport into target cells to improve the efficacy of gene silencing.

The present invention provides, among other things, methods of treating Pompe disease, including administering to a subject in need of treatment a composition comprising an mRNA encoding acid alpha-glucosidase (GAA) at an effective dose and an administration interval such that at least one symptom or feature of Pompe disease is reduced in intensity, severity, or frequency or has delayed in onset. In some embodiments, the mRNA is encapsulated in a liposome comprising one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids and one or more PEG-modified lipids.

Provided are delivery vehicles, and methods of making and using same for reaching epithelial cells, such as cells within mucus-containing environments, and delivery vehicles with improved stability in harsh environments, including in the gastrointestinal tract.

The present disclosure provides a compound that exerts an anticancer action based on CHK1 inhibition. The present disclosure was completed by finding that a compound represented by formula (1) or a pharmaceutically acceptable salt thereof exhibits an excellent antitumor action by having a potent inhibitory action against CHK1:

##STR00001##

wherein R.sup.1, R.sup.2, L, V, W, and Q are as defined herein, X, Y, and Z each independently represent CR.sup.8 or a nitrogen atom, wherein X, Y, and Z are not simultaneously CR.sup.8, and R.sup.8 is as defined herein.

The present invention relates to a liposomal composition for use as a medicament. In particular, the present invention relates to a liposomal composition for use in prevention or early treatment of pathogenic infection. More specifically, the liposomal composition is used for prevention, or early treatment, of pathogenic infection in the respiratory tract, preferably by nasal or pulmonary administration.

Disclosed herein are circular RNAs and transfer vehicles, along with related compositions and methods of treatment. The circular RNAs can comprise group I intron fragments, spacers, an IRES, duplex forming regions, and/or an expression sequence, thereby having the features of improved expression, functional stability, low immunogenicity, ease of manufacturing, and/or extended half-life compared to linear RNA. Pharmaceutical compositions comprising such circular RNAs and transfer vehicles are particularly suitable for efficient protein expression in immune cells in vivo. Also disclosed are precursor RNAs and materials useful in producing the precursor or circular RNAs, which have improved circularization efficiency and/or are compatible with effective circular RNA purification methods.