Abstract: Described herein are block copolymers, and methods of making and utilizing such copolymers. The described block copolymers are disruptive of a cellular membrane, including an extracellular membrane, an intracellular membrane, a vesicle, an organelle, an endosome, a liposome, or a red blood cell. Preferably, in certain instances, the block copolymer disrupts the membrane and enters the intracellular environment. In specific examples, the block copolymer is endosomolytic and capable of delivering an oligonucleotide (e.g., an mRNA) to a cell. Compositions comprising a block copolymer and an oligonucleotide (e.g., an mRNA) are also disclosed.

Abstract: Disclosed are branched PEG molecules, including branched PEG-lipids and branched-PEG proteins, as well as related compositions and methods for making branched PEG molecules. Also disclosed are related compositions, systems, and methods for in vivo delivery of therapeutic and diagnostic agents.

Abstract: Disclosed are methods for delivering a therapeutic or diagnostic agent to the cytosol of a cell in a subject. The disclosed methods generally include administering to the subject an effective amount of a lipid nanoparticle comprising the therapeutic or diagnostic agent and an effective amount of a membrane-destabilizing polymer. Also disclosed are related compositions and delivery systems.

Abstract: Disclosed are methods for delivering a therapeutic or diagnostic agent to the cytosol of a cell in a subject. The disclosed methods generally include administering to the subject an effective amount of a lipid nanoparticle comprising the therapeutic or diagnostic agent and an effective amount of a membrane-destabilizing polymer. Also disclosed are related compositions and delivery systems.

Abstract: Described herein are block copolymers, and methods of making and utilizing such copolymers. The described block copolymers are disruptive of a cellular membrane, including an extracellular membrane, an intracellular membrane, a vesicle, an organelle, an endosome, a liposome, or a red blood cell. Preferably, in certain instances, the block copolymer disrupts the membrane and enters the intracellular environment. In specific examples, the block copolymer is endosomolytic and capable of delivering an oligonucleotide (e.g., an mRNA) to a cell. Compositions comprising a block copolymer and an oligonucleotide (e.g., an mRNA) are also disclosed.

Abstract: Described herein are block copolymers, and methods of making and utilizing such copolymers. The described block copolymers are disruptive of a cellular membrane, including an extracellular membrane, an intracellular membrane, a vesicle, an organelle, an endosome, a liposome, or a red blood cell. Preferably, in certain instances, the block copolymer disrupts the membrane and enters the intracellular environment. In specific examples, the block copolymer is endosomolytic and capable of delivering an oligonucleotide (e.g., an mRNA) to a cell. Compositions comprising a block copolymer and an oligonucleotide (e.g., an mRNA) are also disclosed.

Abstract: Described herein are block copolymers, and methods of making and utilizing such copolymers. The described block copolymers are disruptive of a cellular membrane, including an extracellular membrane, an intracellular membrane, a vesicle, an organelle, an endosome, a liposome, or a red blood cell. Preferably, in certain instances, the block copolymer disrupts the membrane and enters the intracellular environment. In specific examples, the block copolymer is endosomolytic and capable of delivering an oligonucleotide (e.g., an mRNA) to a cell. Compositions comprising a block copolymer and an oligonucleotide (e.g., an mRNA) are also disclosed.

Abstract: Disclosed are branched PEG molecules, including branched PEG-lipids and branched-PEG proteins, as well as related compositions and methods for making branched PEG molecules. Also disclosed are related compositions, systems, and methods for in vivo delivery of therapeutic and diagnostic agents.

Abstract: Described herein are block copolymers, and methods of making and utilizing such copolymers. The described block copolymers are disruptive of a cellular membrane, including an extracellular membrane, an intracellular membrane, a vesicle, an organelle, an endosome, a liposome, or a red blood cell. Preferably, in certain instances, the block copolymer disrupts the membrane and enters the intracellular environment. In specific examples, the block copolymer is endosomolytic and capable of delivering an oligonucleotide (e.g., an mRNA) to a cell. Compositions comprising a block copolymer and an oligonucleotide (e.g., an mRNA) are also disclosed.

Abstract: This disclosure provides a range of amino acid lipid compounds and compositions useful for drug delivery, therapeutics, and the diagnosis and treatment of diseases and conditions. The amino acid lipid compounds and compositions can be used for delivery of various agents such as nucleic acid therapeutics to cells, tissues, organs, and subjects.

Abstract: Described herein are block copolymers, and methods of making and utilizing such copolymers. The described block copolymers are disruptive of a cellular membrane, including an extracellular membrane, an intracellular membrane, a vesicle, an organelle, an endosome, a liposome, or a red blood cell. Preferably, in certain instances, the block copolymer disrupts the membrane and enters the intracellular environment. In specific examples, the block copolymer is endosomolytic and capable of delivering an oligonucleotide (e.g., an mRNA) to a cell. Compositions comprising a block copolymer and an oligonucleotide (e.g., an mRNA) are also disclosed.

Abstract: Disclosed are methods for delivering a therapeutic or diagnostic agent to the cytosol of a cell in a subject. The disclosed methods generally include administering to the subject an effective amount of a lipid nanoparticle comprising the therapeutic or diagnostic agent and an effective amount of a membrane-destabilizing polymer. Also disclosed are related compositions and delivery systems.

Abstract: This invention provides single-stranded and multi-stranded compounds that are useful in various therapeutic modalities to regulate the expression of nucleic acid molecules in a cell. A range of compounds is provided, each containing one or more conformationally restricted nucleomonomers (CRN). In addition, compounds can contain one or more conformationally restricted nucleomonomers and one or more hydroxymethyl substituted nucleomonomers (unlocked nucleomonomers, UNA).

Abstract: Described herein are block copolymers, and methods of making and utilizing such copolymers. The described block copolymers are disruptive of a cellular membrane, including an extracellular membrane, an intracellular membrane, a vesicle, an organelle, an endosome, a liposome, or a red blood cell. Preferably, in certain instances, the block copolymer disrupts the membrane and enters the intracellular environment. In specific examples, the block copolymer is endosomolytic and capable of delivering an oligonucleotide (e.g., an mRNA) to a cell. Compositions comprising a block copolymer and an oligonucleotide (e.g., an mRNA) are also disclosed.

Abstract: Lipopeptide compounds having a central peptide HHHHHKHHHKKKHKHKKK (SEQ ID NO:15) and a lipophilic group attached to each terminus of the peptide, and salts thereof. The lipopeptides are useful for forming pharmaceutical compositions for delivery of nucleic acid agents, such as siRNA and mdRNA agents, as well as in methods for treating the signs and symptoms of disease.

Abstract: Processes for synthesis of conformationally restricted nucleomonomers (CRN) by ozonolysis or oxidation of a 2?-vinyl substituted nucleoside precursor with protected 3?-hydroxyl, 4?-hydroxymethyl and 5?-hydroxyl positions. The CRN nucleomonomers can be used to prepare nucleic acid compounds. CRN nucleomonomers for nucleic acid compounds can be prepared in high yields and in multi-gram scale. The nucleic acid compounds can be of various regulatory classes such as antisense RNA for therapeutic modalities useful for treating or preventing diseases or disorders by up- or down-regulating the expression of genes and other nucleic acid based regulatory systems in a cell.

Abstract: This disclosure provides a range of tyrosine amino acid lipid compounds and compositions useful for drug delivery, therapeutics, and the diagnosis and treatment of diseases and conditions. The amino acid lipid compounds and compositions can be used for delivery of various agents such as nucleic acid therapeutics to cells, tissues, organs, and subjects.

Abstract: Activity-generating delivery molecules comprising the structure R3—(C?O)-Xaa-NH—R4 wherein Xaa is any D- or L-amino acid residue with a non-hydrogen, substituted or unsubstituted side chain, R3—(C?O)— and —NH—R4 are independently a long chain group, each long chain group containing one or more carbon-carbon double bonds, and salts, compositions and methods of use thereof. The activity-generating delivery compounds and compositions are useful for generating activity of an active agent in a cell, tissue, or subject.

Abstract: This invention provides oligomer structures for therapeutic agents, the oligomers composed of one or more UNA nucleomonomers, along with nucleic acid monomers. The UNA oligomers may be used as therapeutic agents for treating or preventing disease. The UNA oligomers can be capable of modulating or silencing gene expression, through RNA interference or other modalities, and may have an antisense strand and a sense strand.

Abstract: Described herein are block copolymers, and methods of making and utilizing such copolymers. The described block copolymers are disruptive of a cellular membrane, including an extracellular membrane, an intracellular membrane, a vesicle, an organelle, an endosome, a liposome, or a red blood cell. Preferably, in certain instances, the block copolymer disrupts the membrane and enters the intracellular environment. In specific examples, the block copolymer is endosomolytic and capable of delivering an oligonucleotide (e.g., an mRNA) to a cell. Compositions comprising a block copolymer and an oligonucleotide (e.g., an mRNA) are also disclosed.