Covalently linked linear polyethylenimine (PEI) clusters are provided that change conformation depending upon changes in counterion concentrations. The structures may be used for the storage, delivery, and/or transport of substances.

Disclosed are methods of treating cancer of the intraperitoneal cavity using compositions comprising nanoparticles without targeting agents. In addition, nanoparticles are described that comprise a highly toxic anticancer agent (e.g., an anticancer agent having an IC.sub.50 less than 1 nM) covalently bound via a linker to a triblock copolymer. Other nanoparticles that comprise Pt(IV) and an anticancer agent are also described. Also disclosed are nanoparticles comprising imaging agents non-covalently associated with a polymer, and methods of imaging cancer of the intraperitoneal cavity using compositions comprising nanoparticles without targeting agents.

Provided herein are micellic assemblies comprising a plurality of copolymers. In certain instauces, micellic assemblies provided herein are pH sensitive particles.

Poly(amine-co-ester) polymers, methods of forming active agent-load polyplexes and particles therefrom, and methods of using them for delivery of nucleic acid agents with optimal uptake have been developed. Examples demonstrate critical molecular weights in combination with exposed carboxylic and/or hydroxyl groups, and methods of making. Typically, the compositions are less toxic, more efficient at drug delivery, or a combination thereof compared to a control other transfection reagents. In some embodiments, the compositions are suitable for in vivo delivery, and can be administered systemically to a subject to treat a disease or condition. For poly(amine-co-ester) polymers with specific amine or hydroxyl group containing end-groups in admixture with PEGylated poly(amine-co-ester) polymers, in vivo delivery to the lung by inhalation has been shown.

Disclosed herein are novel methods for administration of rAAV particles having enhanced transduction properties, comprising the pre-incubation and co-administration of AAV capsids and polyvinyl alcohol (PVA). The disclosed methods of rAAV particle administration have improved efficiency in transducing mammalian liver and hematopoetic cells in vivo. The disclosed methods are suitable for use with a variety of AAV capsid serotypes and presudotypes and improve vector potency, thus lowering the concentration of rAAV particle required to achieve the desired effect. Further disclosed herein are buffers for storage and manufacturing of rAAV particles comprising PVA.

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.

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.

A novel class of fusion proteins to recruit a cell's innate chaperone mechanism, specifically the Hsp70-mediated system, to specifically reduce polyglutamine-mediated protein aggregation is disclosed.

The application relates to the use of loaded red blood cells (e.g. “RBCs”, “red cells” or “erythrocytes”) or red blood cell precursors to produce red cell extracellular vesicles (RCEVs) containing cargos, including cargos comprising biologically active ingredients. Notable red cell precursors include hematopoietic stem cells (HSCs), induced pluripotent stem cells (iPSCs), and reticulocytes. The cargo may comprise nucleic acids, proteins, small molecules, or components of a gene editing system, including CRISPR/Cas9. The RCEVs may be used to treat of diseases and disorders including autoimmune disorders, cancers, cardiovascular diseases, gastrointestinal diseases, genetic disorders, or inflammatory diseases. The RCEVs may also be used to carry antigens and or immune modulator, for use in eliciting immune or immune tolerance responses. Also provided are methods for producing cargo loaded RCEVs (CLRCEVs) by first loading cargo into red cells and then by vesiculating the cargo loaded red cells to yield the CLRCEVs.

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.