Abstract: Provided herein is an ionizable, cationic amino lipid or a pharmaceutically acceptable salt thereof. The ionizable, cationic amino lipid has: a protonatable amino head group; two lipophilic chains, wherein the protonatable amino head group has a central carbon atom to which each of the two lipophilic chains are directly bonded; at least one of the two lipophilic chains has a structure of Formula C: wherein E is an ester in either orientation. The compounds may be formulated in a lipid nanoparticle for use in the delivery of charged cargo such as nucleic acid.

Abstract: Provided is lipid and methods of making such lipid, the lipid having the structure of: each R is independently an alkyl of C12 to C16, each alkyl having 1 to 3 C?C double bonds, wherein at least one of the double bonds is of Z geometry; R? is an optional alkyl; W is O, NH or NR?, wherein R? is a C1 to C3 alkyl group, such as a methyl; X is either absent or present, and if present, X is O, NH, or the NR?; and Z is an alkylamino chain as defined by [—(CH2)m—NG1G2G3], wherein m is 1-5 and G1 and G2 are, independently, the C1 to C3 alkyl group, G3 is absent, a hydrogen or the C1 to C3 alkyl group.

Abstract: The present disclosure provides a lipid nanoparticle comprising encapsulated mRNA and at least 30 mol % of a sphingolipid (e.g. sphingomyelin (SM)), and at least one of a sterol and a hydrophilic polymer-lipid conjugate, the lipid nanoparticle comprising a core comprising an electron dense region and an aqueous portion surrounded at least partially by a lipid layer comprising a bilayer and the lipid nanoparticle exhibiting at least a 2-fold increase in gene expression in the liver, spleen and/or bone marrow at 4 or 24 hours post-injection as compared to a lipid nanoparticle encapsulating mRNA with an Onpattro™-type formulation of cationic, ionizable lipid/DSPC or ESM/cholesterol/PEG-lipid at 50/10/38.5/1.5, mol:mol, wherein the gene expression is measured in an animal model by detection of green fluorescent protein (GFP). Further provided are methods of medical treatment and uses of such lipid nanoparticles to treat or prevent a disease condition in a hepatic or non-hepatic tissue or organ.

Abstract: Provided herein is an ionizable, cationic amino lipid or a pharmaceutically acceptable salt thereof. The ionizable, cationic amino lipid has: a protonatable amino head group; two lipophilic chains, wherein the protonatable amino head group has a central carbon atom to which each of the two lipophilic chains are directly bonded; at least one of the two lipophilic chains has a structure of Formula C: wherein E is an ester in either orientation. The compounds may be formulated in a lipid nanoparticle for use in the delivery of charged cargo such as nucleic acid.

Abstract: The present invention provides a method for preparing a micrococcin-based carboxylic acid compound and a micrococcin-based carboxylic acid compound prepared thereby, and the method for preparing a micrococcin-based carboxylic acid compound according to the present invention enables easy introduction of various functional groups by introducing a carboxyl group into a micrococcin compound.

Abstract: Provided is lipid and methods of making such lipid having the structure of Formula A: each R is an alkyl having a carbon backbone of C12 to C16 having 1 to 3 C?C double bonds, at least one having Z-geometry; R? is an optional alkyl of C2 to C24 having 0 to 3 C?C double bonds; each R, and the R? alkyl group if present, is optionally substituted at one or more positions with a C1 to C3 alkyl; W and X are O or S; Y is absent and C1 and C2 are bonded, or Y is present and is a metheno, etheno or ethyno bridge optionally substituted with an alkylamino chain [—(CH2)m—NG1G2G3], wherein m is 1-5 and G1, G2 are, independently, C1 to C3 alkyl, G3 is absent, hydrogen or C1 to C3 alkyl, or wherein NG1G2G3 is a heterocycle; and Z and Z? are H or alkylamino.

Abstract: Provided herein is a method for the preparation of ionizable, cationic amino lipids using a doubly alkylated nucleophilic intermediate to produce a ketone. The ketone, or a corresponding alcohol, is subjected to one or more synthesis steps to add an ionizable moiety thereto. The method can be advantageously employed for the synthesis of unsymmetrical analogues of the above lipids that would be considerably more difficult to make by alternative strategies. The method can also be used to prepare symmetrical ionizable, cationic amino lipids with fewer steps and/or with the use of fewer hazardous chemicals than known synthesis methods.

Abstract: Provided herein is a method for producing an ionizable lipid that comprises: (i) reacting fatty esters in a Claisen condensation reaction in the presence of a catalyst, the Claisen condensation employing a weak base and carried out at a temperature of between ?10 and 60 degrees Celsius to produce a ketoester; (ii) reacting the ketoester produced in step (i) under conditions to produce a ketone from the ketoester in one or more steps via a hydrolysis and decarboxylation of the ketoester; and (iii) preparing the ionizable lipid from the ketone thereof using one or more synthesis steps resulting in an addition of an ionizable head group moiety to (a) the ketone; or (b) an alcohol produced from an optional reduction of the ketone to produce the alcohol, thereby producing the ionizable lipid. The ionizable lipid produced in step (iii) may be formulated in a drug delivery vehicle.

Abstract: The present invention provides a method for preparing a micrococcin compound, and a pharmaceutical composition for the treatment and prevention of infection of a specific strain comprising a micrococcin compound, a solvate thereof, a hydrate thereof, a prodrug thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof as effective component. In addition, the present invention provides an anti-inflammatory composition comprising the micrococcin compound, a solvate thereof, a hydrate thereof, a prodrug thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof as an effective component.

Abstract: Provided herein is an ionizable, cationic amino lipid or a pharmaceutically acceptable salt thereof. The ionizable, cationic amino lipid has: a protonatable amino head group; two lipophilic chains, wherein the protonatable amino head group has a central carbon atom to which each of the two lipophilic chains are directly bonded; at least one of the two lipophilic chains has a structure of Formula C: wherein E is an ester in either orientation. The compounds may be formulated in a lipid nanoparticle for use in the delivery of charged cargo such as nucleic acid.

Abstract: Provided herein is a compound having a structure of Formula (I): (Formula (I)) wherein: D is S, O or an ester; p is 1 to 6; L1 and/or L2 are independently linear or branched C1-C30 alkyl, optionally having one or more C?C double bonds of E or Z geometry; and wherein: if D is S then L1 and/or L2 are unsubstituted or substituted with one or more S; and if D is O or an ester, then L1 and/or L2 are substituted with one more S. The compound may be formulated in a lipid nanoparticle for use in the delivery of charged cargo such as nucleic acid. Further provided are methods for making the compound.

Abstract: The present invention provides a novel compound, a solvate thereof, a hydrate thereof, a prodrug thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof, a preparation method thereof, and an antibiotic composition comprising the same. The novel compound of the present invention having excellent antimicrobial activity is very useful for preventing and treating a bacterial infection.

Abstract: Disclosed herein is a lipid having a net charge at physiological pH, and being covalently attached to a lipid moiety. The lipid moiety comprises a hydrocarbon structure having two or more linked hydrocarbon chains, optionally having cis or trans C?C, at least one of said chains being covalently attached to the head group optionally via the linker region. The hydrocarbon chains are bonded to one another at a branch point at an internal carbon of the chain attached to the linker region, which branch point comprises a functional group having an electronegative atom. The hydrocarbon chains each have between 1 and 40 carbon atoms, wherein the hydrocarbon structure in total comprises between 10 and 150 carbon atoms. Advantageously, the hydrocarbon structure may assume a generally flared shape for enhanced delivery of cargo molecules. Further provided are delivery vehicles comprising the lipids.

Abstract: The application relates to a lipid conjugate of formula M-X1-L wherein M is a molecule of interest such as a drug moiety; X1 is a linker group such as ester, ether or carbamate; and L is a lipid scaffold represented by formula (IId): -L1-[L2(H)(X2R)]n-L3-[L4(H)(X2R)]p-L5-L6 and wherein L comprises 5 to 40 carbon atoms and 0 to 2 carbon-carbon double bonds. The lipid conjugate can p be formulated in a drug delivery vehicle such as a lipid nanoparticle (LNP).

Abstract: The invention features a method of identifying therapeutically relevant compositions which include a therapeutic agent and 2,2-dimethylaminomethyl-[1-3]-dioxolane by screening for an effect of the agent on the liver of a model subject.

Abstract: This invention provides lipid-linked prodrugs having structures as set out herein. Uses of such lipid-linked prodrug compounds for treatment of various indications, and methods for making and using lipid-linked prodrugs are also provided.

Abstract: The invention features a method of identifying therapeutically relevant compositions which include a therapeutic agent and 2,2-dimethylaminomethyl-[1-3]-dioxolane by screening for an effect of the agent on the liver of a model 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: This invention provides lipid-linked prodrugs having structures as set out herein. Uses of such lipid-linked prodrug compounds for treatment of various indications, and methods for making and using lipid-linked prodrugs are also provided.

Abstract: Drag derivatives are provided herein which are suitable for loading into liposomal nanoparticle carriers. In some preferred aspects, the derivatives comprise a poorly water-soluble drag derivatized with a weak-base moiety that facilitates active loading of the drag through a LN transmembrane pH or ion gradient into the aqueous interior of the LN. The weak-base moiety can optionally comprise a lipophilic domain that facilitates active loading of the drag to the inner monolayer of the liposomal membrane. Advantageously, LN formulations of the drag derivatives exhibit improved solubility, reduced toxicity, enhanced efficacy, and/or other benefits relative to the corresponding free drags.