Abstract: Provided herein are compounds of Formula (I), and salts thereof, wherein each instance of RL is independently optionally substituted C6-C40 alkenyl. Further provided are compositions comprising a compound of Formula (I) and an agent. Further provided are methods and kits using the compositions for delivering an agent to a subject or cell and for treating and/or preventing a range of diseases. Further provided are methods of preparing compounds of Formula (I) and precursors thereof.

Abstract: Provided herein are lipidoid compounds of Formulae (I) and (II), and pharmaceutically acceptable salts, co-crystals, tautomers, stereoisomers, solvates, hydrates, polymorphs, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive lipidoid compounds, compositions, or formulations for treating and/or preventing diseases (e.g., genetic disease, proliferative disease, hematological disease, neurological disease, painful condition, psychiatric disorder, metabolic disorder, long-term medical condition, inflammatory disease, autoinflammatory disease, liver disease, lung disease, spleen disease, familial amyloid neuropathy, cardiovascular disease, viral infection, infectious disease, fibrotic condition, or autoimmune disease) in a subject, methods for synthesizing the compounds described herein, and compounds described herein synthesized by the synthetic methods described herein.

Abstract: Provided herein are branched poly(beta-amino esters) (PBAE) useful as vehicles for the delivery of therapeutic agents, such as nucleic acids. The disclosed polymers form stable compositions, and are suitable for the delivery of therapeutic agents via nebulization. Compositions of the disclosed polymers are capable of delivering therapeutic agents such as mRNA to lung epithelial cells.

Abstract: Provided herein are compounds of Formula (I), and salts thereof, wherein each instance of RL is independently optionally substituted C6-C40 alkenyl. Further provided are compositions comprising a compound of Formula (I) and an agent. Further provided are methods and kits using the compositions for delivering an agent to a subject or cell and for treating and/or preventing a range of diseases. Further provided are methods of preparing compounds of Formula (I) and precursors thereof.

Abstract: Provided herein are compounds, such as compounds of Formula (I), and pharmaceutically acceptable salts, hydrates, solvates, polymorphs, co-crystals, tautomers, stereoisomers, and isotopically labeled derivatives thereof, and compositions, methods, uses, and kits thereof. The compounds provided herein are lipids useful for delivery of polynucleotides, such as mRNA, for the treatment and/or prevention of various diseases and conditions (e.g., genetic disease, proliferative disease, hematological disease, neurological disease, liver disease, spleen disease, lung disease, painful condition, psychiatric disorder, musculoskeletal disease, a metabolic disorder, inflammatory disease, or autoimmune disease).

Abstract: Described herein are compounds and compositions characterized, in certain embodiments, by conjugation of various groups, such as lipophilic groups, to an amino or amide group of an amino acid, a linear or cyclic peptide, a linear or cyclic polypeptide, or structural isomer thereof, to provide compounds of the present invention, collectively referred to herein as “APPLs”. Such APPLs are deemed useful for a variety of applications, such as, for example, improved nucleotide delivery. Exemplary APPLs include, but are not limited to, compounds of Formula (I), (II), (III), (IV), (V), and (VI), and salts thereof, as described herein: wherein m, n, p, R?, R1, R2, R3, R4, R5, R8, Z, W, Y, and Z are as defined herein.

Abstract: The present disclosure relates to improvements in the selection and formulation of PBAE polymers using a design of experiment approach, in which statistical methods are used to limit possible experimental conditions. The present disclosure relates to improved PBAE polymers and formulations.

Abstract: Provided herein are branched poly(beta-amino esters) (PBAE) useful as vehicles for the delivery of therapeutic agents, such as nucleic acids. The disclosed polymers form stable compositions, and are suitable for the delivery of therapeutic agents via nebulization. Compositions of the disclosed polymers are capable of delivering therapeutic agents such as mRNA to lung epithelial cells.

Abstract: Provided herein are branched poly(beta-amino esters) (PBAE) useful as vehicles for the delivery of therapeutic agents, such as nucleic acids. The disclosed polymers form stable compositions, and are suitable for the delivery of therapeutic agents via nebulization. Compositions of the disclosed polymers are capable of delivering therapeutic agents such as mRNA to lung epithelial cells.

Abstract: Described herein are compounds and compositions characterized, in certain embodiments, by conjugation of various groups, such as lipophilic groups, to an amino or amide group of an amino acid, a linear or cyclic peptide, a linear or cyclic polypeptide, or structural isomer thereof, to provide compounds of the present invention, collectively referred to herein as “APPLs”. Such APPLs are deemed useful for a variety of applications, such as, for example, improved nucleotide delivery. Exemplary APPLs include, but are not limited to, compounds of Formula (I), (II), (III), (IV), (V), and (VI), and salts thereof, as described herein: wherein m, n, p, R?, R1, R2, R3, R4, R5, R8, Z, W, Y, and Z are as defined herein.

Abstract: Provided herein are lipidoid compounds of Formulae (I) and (II), and pharmaceutically acceptable salts, co-crystals, tautomers, stereoisomers, solvates, hydrates, polymorphs, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive lipidoid compounds, compositions, or formulations for treating and/or preventing diseases (e.g., genetic disease, proliferative disease, hematological disease, neurological disease, painful condition, psychiatric disorder, metabolic disorder, long-term medical condition, inflammatory disease, autoinflammatory disease, liver disease, lung disease, spleen disease, familial amyloid neuropathy, cardiovascular disease, viral infection, infectious disease, fibrotic condition, or autoimmune disease) in a subject, methods for synthesizing the compounds described herein, and compounds described herein synthesized by the synthetic methods described herein.

Abstract: Aminoalcohol lipidoids are prepared by reacting an amine with an epoxide-terminated compound are described. Methods of preparing aminoalcohol lipidoids from commercially available starting materials are also provided. Aminoalcohol lipidoids may be prepared from racemic or stereochemically pure epoxides. Aminoalcohol lipidoids or salts forms thereof are preferably biodegradable and biocompatible and may be used in a variety of drug delivery systems. Given the amino moiety of these aminoalcohol lipidoid compounds, they are particularly suited for the delivery of polynucleotides. Complexes, micelles, liposomes or particles containing the inventive lipidoids and polynucleotide have been prepared. The inventive lipidoids may also be used in preparing microparticles for drug delivery. They are particularly useful in delivering labile agents given their ability to buffer the pH of their surroundings.

Abstract: Provided herein are new cyclodextrin-based compounds, and pharmaceutically acceptable salts, stereoisomers, and isotopically labeled derivatives thereof, which are capable of binding sugars (e.g., glucose). The compounds provided herein may be conjugated to agents or tags (e.g., therapeutic agents such as insulin) to form conjugates. In another aspect, also provided herein are pharmaceutical compositions comprising the compounds and conjugates described herein. The compounds and conjugates described herein are capable of binding glucose; therefore, provided herein are methods of sensing or detecting glucose comprising contacting glucose with the compound or conjugate. In another aspect, also provided herein are methods of treating a disease (e.g., a metabolic disorder, such as diabetes) in a subject comprising administering to the subject a compound, conjugate, or composition provided herein.

Abstract: The modification of biomolecules, small molecules, and other agents of via conjugation of excipients, tags, or labels is of great importance. For example, the modification of therapeutic agents can confer improved stability, solubility, duration of action, or pharmacological properties. Supramolecular chemistry utilizes specific, directional, reversible, non-covalent molecular recognition motifs in order to achieve organization of molecules, and can be used to complex tags to agents of interest (e.g., insulin, glucagon, antibodies). The present invention provides useful supramolecular complexes wherein an agent of interest is specifically bound to a host via non-covalent interactions, and wherein the host is conjugated to a tag. The present invention also provides methods and compounds useful in preparing supramolecular complexes, and methods of treating diseases using the supramolecular complexes.

Abstract: Disclosed are methods, compositions, reagents, systems, and kits to prepare and utilize poly (?-amino ester) (PBAE) polymers, which are synthesized via Michael addition reactions of diacrylates and amines disclosed herein. Various embodiments utilize lactones and lactone derivatives to generate the diacrylate compounds. The PBAE polymers are shown to be effective biodegradable carriers for the delivery of an agent such as an organic molecule, inorganic molecule, nucleic acid, protein, peptide, polynucleotide, targeting agent, an isotopically labeled chemical compound, vaccine, or an immunological agent.

Abstract: The modification of biomolecules, small molecules, and other agents of via conjugation of excipients, tags, or labels is of great importance. For example, the modification of therapeutic agents can confer improved stability, solubility, duration of action, or pharmacological properties. Supramolecular chemistry utilizes specific, directional, reversible, non-covalent molecular recognition motifs in order to achieve organization of molecules, and can be used to complex tags to agents of interest (e.g., insulin, glucagon, antibodies). The present invention provides useful supramolecular complexes wherein an agent of interest is specifically bound to a host via non-covalent interactions, and wherein the host is conjugated to a tag. The present invention also provides methods and compounds useful in preparing supramolecular complexes, and methods of treating diseases using the supramolecular complexes.

Abstract: The present invention provides inventive conjugated polyethyleneimine (PEI) polymers and conjugated aza-macrocycles (collectively referred to herein as “conjugated lipomers” or “lipomers”) containing one or more groups of the formula (iii): wherein R3 and R4 are as defined herein. Also provided are compositions comprising the inventive conjugated lipomers, and methods of preparation and use.

Abstract: Disclosed are methods, compositions, reagents, systems, and kits to prepare and utilize poly (?-amino ester) (PBAE) polymers, which are synthesized via Michael addition reactions of diacrylates and amines disclosed herein. Various embodiments utilize lactones and lactone derivatives to generate the diacrylate compounds. The PBAE polymers are shown to be effective biodegradable carriers for the delivery of an agent such as an organic molecule, inorganic molecule, nucleic acid, protein, peptide, polynucleotide, targeting agent, an isotopically labeled chemical compound, vaccine, or an immunological agent.

Abstract: Aminoalcohol lipidoids are prepared by reacting an amine with an epoxide-terminated compound are described. Methods of preparing aminoalcohol lipidoids from commercially available starting materials are also provided. Aminoalcohol lipidoids may be prepared from racemic or stereochemically pure epoxides. Aminoalcohol lipidoids or salts forms thereof are preferably biodegradable and biocompatible and may be used in a variety of drug delivery systems. Given the amino moiety of these aminoalcohol lipidoid compounds, they are particularly suited for the delivery of polynucleotides. Complexes, micelles, liposomes or particles containing the inventive lipidoids and polynucleotide have been prepared. The inventive lipidoids may also be used in preparing microparticles for drug delivery. They are particularly useful in delivering labile agents given their ability to buffer the pH of their surroundings.

Abstract: The present invention provides inventive conjugated polyethyleneimine (PEI) polymers and conjugated aza-macrocycles (collectively referred to herein as “conjugated lipomers” or “lipomers”) containing one or more groups of the formula (iii): wherein R3 and R4 are as defined herein. Also provided are compositions comprising the inventive conjugated lipomers, and methods of preparation and use.