The invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and/or modulation of a cell's status, function, and/or activity.

Described herein is a nanoparticle system including a multivalent nanoparticle core having a plurality of β-hairpin peptides conjugated thereto. Also included are pharmaceutical compositions and methods of making the nanoparticle system. Further included are immunotherapy methods including administering the nanoparticle system to a subject in need thereof, such as a human cancer patient.

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.

Described herein are ultra-deformable liposomes comprising a first lipid and second lipid. The first lipid comprises a first hydrophilic head linked to a first aliphatic tail, and the second lipid comprises a second hydrophilic head linked to a second aliphatic tail having at least two carbons less than the first aliphatic tail. The ultra-deformable liposomes described herein are useful, for example, as drug delivery vehicles. Accordingly, also described herein are compositions comprising an ultra-deformable liposome and a cargo, such as a drug, as well as methods for delivering a drug, such as an anti-cancer therapeutic, to a tumor.

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.

The compounds disclosed herein (e.g., compounds having a structure according to Formula (I), (II), (III), (IV), and (V)) are polymers wherein an organic polymeric segment (e.g., a polyethylene glycol (PEG) group) comprises covalent attachments to two or more lipid substructures, and each lipid substructure independently comprises a hydrophobic moiety and a hydrophilic moiety. The compounds provided herein can be useful for delivery and expression of mRNA and encoded protein, e.g., as a component of liposomal delivery vehicle, and accordingly can be useful for treating various diseases, disorders and conditions, such as those associated with deficiency of one or more proteins.

Milk fat globule membrane (MFGM) phospholipid compositions, methods of preparing and using the MFGM phospholipid compositions, liposomes comprising the MFGM phospholipid compositions, and methods of preparing and using the liposomes comprising the MFGM phospholipid compositions. In various examples, a MFGM phospholipid composition is formed by sequential supercritical carbon dioxide (SC—CO.sub.2) extraction of a milk product and extraction of the remaining milk product with a polar compound-modified SC—CO.sub.2 extraction, where the extract is the MFGM. In various examples, the MFGM is used to prepare liposomes. In various examples, the liposomes are prepared by expansion of a supercritical solution comprising the MFGM composition. In various examples, the liposomes are used to administer a cargo, such as, for example, hydrophilic compound(s), hydrophobic compound(s), amphiphilic compound(s), or the like, any one or all of which may be therapeutic agent(s), nutrient(s), bioagent(s), or the like, or any combination thereof to a subject.

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.

A method for inhibiting expression of an mRNA having an expanded trinucleotide repeat region is provided comprising administering an oligomer comprising a sense strand and an antisense strand wherein: a) the antisense strand comprises a sequence of Formula (I): rGrCrUrGrCrUrGrCX.sup.1X.sup.2rCrUrGrCrUrGrCrUrG (I), wherein X.sup.1 and X.sup.2 are each independently selected from rA, rU, rG, rC, UNA-A, UNA-U, UNA-G, and UNA-C and wherein at least one of X.sup.1 and X.sup.2 is a UNA monomer; b) the oligomer comprises a UNA monomer at the first position at the 5′-end of the sense strand; and the sense strand and the antisense strand each independently include 19-29 monomers. The oligomer can be formulated in a lipid delivery vehicle, and can inhibit expression of Atrophin-1, Huntingtin, Ataxin-1, Ataxin-2, Ataxin-3, Ataxin-7, Alpha1A-voltage-dependent calcium channel subunit, TATA-box binding protein (TBP), Androgen Receptor, PP2A-PR55beta, FMR-1 Protein (FMRP), FMR-2 protein, Frataxin, Dystrophy Protein Kinase (DMPK), or Ataxin-8.

The present application provides a method for preparing a hydrogel and the obtained hydrogel. The method including: forming a first part by mixing a first single-stranded nucleotide with a first liposome, and forming a second part by mixing a second single-stranded nucleotide with a second liposome, wherein the first single-stranded nucleotide and the second single-stranded nucleotide have complementary sticky ends; forming a hydrogel by mixing the first part and the second part.