Abstract: Limit size lipid nanoparticles, methods for using the lipid nanoparticles, and methods and systems for making limit size lipid nanoparticles.

Abstract: The present invention provides superior compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of specific target proteins at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.

Abstract: Transfection reagent composition, lipid nanoparticles prepared from the transfection reagent composition, kits that include the transfection reagent composition, and methods for making and using lipid nanoparticles prepared from the transfection reagent composition. Lipids when dispersed in aqueous media readily form liposomes, such as unilamellar vesicles and multilamellar vesicles. Liposomes have been used successfully to encapsulate and deliver a wide range of chemicals including nucleic acids, proteins and. small molecule drugs, to cells.

Abstract: The present invention provides superior compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of specific target proteins at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.

Abstract: Various lipid nanoparticles are disclosed, including nanoparticles comprising a lipid bilayer comprising a phospholipid, a sterol, a polyethylene glycol-lipid surrounding an aqueous core which comprises a therapeutic and/or diagnostic agent and nanoparticles comprising a lipid monolayer surrounding a hydrophobic core. Of particular interest are limit size lipid nanoparticles with a diameter from 10-100 nm. Such lipid nanoparticles are the smallest particles possible for a specific particle composition. Methods and apparatus for preparing such limit size lipid nanoparticles are disclosed.

Abstract: Fully lipid-encapsulated therapeutic agent particles of a charged therapeutic agent are prepared by combining a lipid composition containing preformed lipid vesicles, a charged therapeutic agent, and a destabilizing agent to form a mixture of preformed vesicles and therapeutic agent in a destabilizing solvent. The destabilizing solvent is effective to destabilize the membrane of the preformed lipid vesicles without disrupting the vesicles. The resulting mixture is incubated for a period of time sufficient to allow the encapsulation of the therapeutic agent within the preformed lipid vesicles. The destabilizing agent is then removed to yield fully lipid-encapsulated therapeutic agent particles. The preformed lipid vesicles comprise a charged lipid which has a charge which is opposite to the charge of the charged therapeutic agent and a modified lipid having a steric barrier moiety for control of aggregation.

Abstract: Fully lipid-encapsulated therapeutic agent particles of a charged therapeutic agent are prepared by combining a lipid composition containing preformed lipid vesicles, a charged therapeutic agent, and a destabilizing agent to form a mixture of preformed vesicles and therapeutic agent in a destabilizing solvent. The destabilizing solvent is effective to destabilize the membrane of the preformed lipid vesicles without disrupting the vesicles. The resulting mixture is incubated for a period of time sufficient to allow the encapsulation of the therapeutic agent within the preformed lipid vesicles. The destabilizing agent is then removed to yield fully lipid-encapsulated therapeutic agent particles. The preformed lipid vesicles comprise a charged lipid which has a charge which is opposite to the charge of the charged therapeutic agent and a modified lipid having a steric barrier moiety for control of aggregation.

Abstract: A lipid particle can include a plurality of cationic lipids, such as a first cationic lipid and a second cationic lipid. The first cationic lipid can be selected on the basis of a first property and the second cationic can be selected on the basis of a second property. The first and second properties are complementary. The attributes of the lipid particle can reflect the selected properties of the cationic lipids, and the complementary nature of those properties.

Abstract: Fully lipid-encapsulated therapeutic agent particles of a charged therapeutic agent are prepared by combining a lipid composition containing preformed lipid vesicles, a charged therapeutic agent, and a destabilizing agent to form a mixture of preformed vesicles and therapeutic agent in a destabilizing solvent. The destabilizing solvent is effective to destabilize the membrane of the preformed lipid vesicles without disrupting the vesicles. The resulting mixture is incubated for a period of time sufficient to allow the encapsulation of the therapeutic agent within the preformed lipid vesicles. The destabilizing agent is then removed to yield fully lipid-encapsulated therapeutic agent particles. The preformed lipid vesicles comprise a charged lipid which has a charge which is opposite to the charge of the charged therapeutic agent and a modified lipid having a steric barrier moiety for control of aggregation.

Abstract: Lipid particles containing a nucleic acid, devices and methods for making the lipid particles, and methods for using the lipid particles.

Abstract: Compositions, methods and compounds useful for enhancing the uptake of a lipid particle b\ a cell are described In particular embodiments, the methods of the invention include contacting a cell with a lipid particle and a compound that binds a Na+/K+ ATPase to enhance uptake of the lipid particle b\ the cell Related compositions useful in practicing methods include lipid particles comprising a conjugated compound that enhances uptake of the lipid particles b\ the cell The methods and compositions are useful in delivering a therapeutic agent to a cell, e g for the treatment of a disease or disorder in a subject

Abstract: The present invention provides superior compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of specific target proteins at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.

Abstract: Methods for the preparation of a lipid-nucleic acid composition are provided. According to the methods, a mixture of lipids containing a protonatable or deprotonatable lipid, for example an amino lipid and a lipid such as a PEG- or Polyamide oligomer-modified lipid is combined with a buffered aqueous solution of a charged therapeutic agent, for example polyanionic nucleic acids, to produce particles in which the therapeutic agent is encapsulated in a lipid vesicle. Surface charges on the lipid particles are at least partially neutralized to provide surface-neutralized lipid-encapsulated compositions of the therapeutic agents. The method permits the preparation of compositions with high ratios of therapeutic agent to lipid and with encapsulation efficiencies in excess of 50%.

Abstract: Fully lipid-encapsulated therapeutic agent particles of a charged therapeutic agent are prepared by combining a lipid composition containing preformed lipid vesicles, a charged therapeutic agent, and a destabilizing agent to form a mixture of preformed vesicles and therapeutic agent in a destabilizing solvent. The destabilizing solvent is effective to destabilize the membrane of the preformed lipid vesicles without disrupting the vesicles. The resulting mixture is incubated for a period of time sufficient to allow the encapsulation of the therapeutic agent within the preformed lipid vesicles. The destabilizing agent is then removed to yield fully lipid-encapsulated therapeutic agent particles. The preformed lipid vesicles comprise a charged lipid which has a charge which is opposite to the charge of the charged therapeutic agent and a modified lipid having a steric barrier moiety for control of aggregation.

Abstract: The present invention provides compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of specific target protein at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.

Abstract: The present invention includes novel liposomes comprising dihydrosphingomyelin. The invention also includes compositions comprising these liposomes and a therapeutic agent, in addition to methods and kits for delivering a therapeutic agent or treating a disease, e.g., a cancer, using these compositions.

Abstract: Plasmid-lipid particles which are useful for transfection of cells in vitro or in vivo are described. The particles can be formed using either detergent dialysis methods or methods which utilize organic solvents. The particles are typically 65-85 nm, fully encapsulate the plasmid and are serum-stable.

Abstract: Novel lipid-nucleic acid particulate complexes which are useful for in vitro or in vivo gene transfer are described. The particles can be formed using either detergent dialysis methods or methods which utilize organic solvents. Upon removal of a solubilizing component (i.e., detergent or an organic solvent) the lipid-nucleic acid complexes form particles wherein the nucleic acid is serum-stable and is protected from degradation. The particles thus formed have access to extravascular sites and target cell populations and are suitable for the therapeutic delivery of nucleic acids.

Abstract: Methods and compositions for triggering the delivery of an encapsulated therapeutic agent from a liposome are provided. Liposomes of opposite charge and incorporating lipids which favor non-lamellar structures are contacted in vivo. At least one of the liposome encapsulates at least one therapeutic drug or agent. Preferably, the liposomes have a fusogenic hydrophillic coating, such as PEG to control the rate of interaction of the liposomes and release of the therapeutic agent.

Abstract: The present invention relates to liposomes and virosomes and, more particularly, to liposomal and virosomal delivery systems for transporting materials such as drugs, nucleic acids and proteins.