44 results about "Peg lipid" patented technology

The invention discloses application of fluorinated ionizable lipid as a gene drug delivery carrier, and belongs to the technical field of biological medicine. The gene drug delivery carrier provided by the invention is prepared from fluorinated ionizable lipids, cationic lipids, auxiliary lipids, structural lipids and PEG lipids, wherein the molar percentage of the fluorinated ionizable lipids in the gene drug delivery carrier is 1%-10%. According to the invention, the molar percentage of the fluorinated ionizable lipid in the total lipid is optimized to 1-10%, so that the cytotoxicity is obviously reduced, and more excellent nucleic acid transfection efficiency is realized in vivo and in vitro; various nucleic acid drugs including DNA, mRNA, siRNA and CRISPR-Cas9 ribonucleoprotein can be efficiently delivered, action targets of the nucleic acid drugs are expanded to cell nucleuses and cytoplasm, and the nucleic acid drugs are more accordant with the action mechanism of modern gene therapy and editing.

The present disclosure relates to compositions comprising lipid nanoparticles (LNPs) configured for targeting dendritic cells. In particular, the present disclosure provides LNPs comprising a serine-based helper-lipid, a PEG lipid, an ionizable lipid, a cholesterol component, and one or more nucleic acids. The present disclosure provides use of the LNPs for the delivery of nucleic acid molecules, specifically mRNA; thereby making them highly suitable for use in various therapeutics, such as for the treatment of cancer or autoimmune diseases or prevention of infectious diseases. Finally, methods are provided for preparing such LNPs.

The invention discloses a macrophage-targeting lipid nanoparticle and application thereof in malignant tumor treatment, ID3 mRNA is delivered through the lipid nanoparticle, firstly, an ID3 sequence is subjected to codon optimization to improve the expression efficiency and stability of ID3 protein, and the core treatment effect is enhanced; the lipid composition and the targeting ligand of the nanoparticles are further optimized, and mannose modified PEG lipid material (DSPE-PEG2000-Mannose) is specifically combined with the CD206 receptor on the surface of the macrophage, so that the targeting property and the transfection efficiency of the delivery system are remarkably improved. The ID3 mRNA is delivered to the macrophages by utilizing the lipid nanoparticles of the targeted macrophages, so that the tumor cells can be effectively swallowed and killed, the in-situ treatment of pancreatic cancer is realized, and better tumor inhibition and immune activation effects are achieved.

The present disclosure provides ionizable lipids and lipid nanoparticle (LNP) compositions comprising ionizable lipids, helper lipids, neutral lipids, and PEG lipids that can be used to deliver bioactive agents, such as to deliver bioactive agents to cells to prepare engineered cells. The LNP compositions disclosed herein are useful in methods of gene editing and methods of delivering bioactive agents, as well as methods of modifying or cleaving DNA.

The invention relates to mRNA comprising lipid nanoparticles and their medical uses. The lipid nanoparticles of the present invention comprise a cationic lipid according to formula (I), (II) or (III) and / or a PEG lipid according to formula (IV), as well as an mRNA compound comprising an mRNA sequence encoding an antigenic peptide or protein. The invention further relates to the use of said lipid nanoparticles as vaccines or medicaments, in particular with respect to influenza or rabies vaccination.

The invention relates to the technical field of preparation of mRNA vaccine lipid nanoparticles, and particularly discloses a whole-process low-temperature rapid mixing preparation method. The method comprises the following steps: dissolving ionizable lipid, auxiliary lipid, cholesterol and PEG lipid in absolute ethyl alcohol containing an anti-freezing agent, and pre-cooling at 0-10 DEG C; dissolving mRNA in a low-ionic-strength acidic buffer solution, and adding a low-temperature protective agent to form a uniform water phase; the preparation method comprises the following steps: mixing LNP in a hydrophilic modified micro-fluidic chip at 0-10 DEG C according to a flow velocity ratio of (2.5-3.5): 1, completing mixing within 10 ms when the Reynolds number is greater than or equal to 2000 and the Weber number is greater than or equal to 100, and then performing low-temperature curing, two-step buffer solution replacement and low-temperature tangential flow filtration to obtain the LNP with the particle size of 70-90 nm, the PDI of less than or equal to 0.15 and the encapsulation efficiency of greater than or equal to 95%. The anti-freezing agent and the protective agent have a synergistic effect, so that ethanol crystallization and ice crystal damage are effectively inhibited, a microchannel is not blocked under a low-temperature condition, the particle size uniformity and mRNA structural integrity are remarkably improved, and the obtained preparation is stable for a long time at the temperature of 4 DEG C and-20 DEG C.

The present invention provides a method for producing nucleic acid-encapsulated ligand-modified lipid nanoparticles, the method comprising the following steps a)-c), etc.: a step a) in which an alcoholic solution containing an ionic lipid, a sterol, and a PEG lipid is mixed with an acidic buffer solution having a pH of 1-6.5 to obtain a suspension of lipid nanoparticles not containing nucleic acid; the method comprises a step b) of mixing nucleic acid-free lipid nanoparticles with a nucleic acid solution to obtain a suspension of nucleic acid-encapsulated lipid nanoparticles, and a step c) of mixing the suspension of nucleic acid-encapsulated lipid nanoparticles with a ligand-bound lipid to obtain a suspension of nucleic acid-encapsulated ligand-modified lipid nanoparticles.

The disclosure provides novel lipids and compositions comprising them. The nanoparticle compositions comprise a novel lipid as well as additional lipids such as phospholipids, structural lipids and PEG lipids. Nanoparticle compositions further comprising therapeutic and / or prophylactic agents such as RNA are useful in delivering therapeutic and / or prophylactic agents to mammalian cells or organs, for example, for modulating polypeptide, protein or gene expression.

A lyophilized composition capable of encapsulating any nucleic acid with high efficiency and easily is provided. A lyophilized composition of lipid nanoparticles not containing a nucleic acid but containing an ionic lipid, a sterol, a PEG lipid, an acidic buffer component that shows a buffering action at pH 1-6, and a cryoprotectant, wherein a weight ratio of the cryoprotectant and a total lipid is 10:1-1000:1.

The present disclosure describes compounds, compositions, and processes for preparing building blocks of GalNAc PEG lipids and purification methods.

A lyophilized composition capable of encapsulating any nucleic acid with high efficiency and easily is provided. A lyophilized composition of lipid nanoparticles not containing a nucleic acid but containing an ionic lipid, a sterol, a PEG lipid, an acidic buffer component that shows a buffering action at pH 1-6, and a cryoprotectant, wherein a weight ratio of the cryoprotectant and a total lipid is 10:1-1000:1.

The present invention relates to a material for local drug delivery and use thereof. Specifically provided is a nanoparticle composition. The nanoparticle composition comprises a cationic lipid, a PEG lipid, and a structural lipid, wherein the lipid component of the PEG lipid is 1.0-5.5 mol%, or a range between any two of the described values. The nanoparticle composition of the present invention is delivered only at the site of administration.

The disclosure features novel lipids and compositions involving the same. Nanoparticle compositions include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Nanoparticle compositions further including therapeutic and / or prophylactics such as RNA are useful in the delivery of therapeutic and / or prophylactics to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.

The present invention pertains to lipid nanoparticles which contains a nucleic acid, a cationic lipid, and a phospholipid and in which: the cationic lipid is one or more selected from the group consisting of cKK-E15, Lipid A4, AA-T3A-C12, Dlin-KC2-DMA, OF-C4-Deg-Lin, and C14-4; the phospholipid is one or more selected from the group consisting of DOPC, DOPE, and DSPC; and the molar ratio of the cationic lipid to the phospholipid content is 0.2-15.0. The present invention also pertains to a method for producing the lipid nanoparticles, the method comprising: a step for preparing a lipid solution containing the cationic lipid, the phospholipid, sterol, and PEG lipid; a step for preparing a nucleic acid solution containing a nucleic acid; and a step for mixing the lipid solution and the nucleic acid solution.

Lipid nanoparticle compositions comprising a payload, a helper lipid, a sterol, a PEG lipid, an ionizable lipid, a permanent cationic lipid are provided. Also provided herein is a method of delivering a payload to cells in the lung of a subject by intravenous administration, and a method of treating and / or preventing a lung disease in a subject in need thereof by intravenous administration. Also provided is a method for quantifying the amount of capped messenger RNA (mRNA) in an mRNA sample, the method comprising contacting the mRNA with two or more of a nuclease, an alkaline phosphatase, and a polynucleotide kinase, and separating the capped mRNA and uncapped mRNA using chromatography.

The present disclosure provides a lipid nanoparticle, the lipid nanoparticle comprises a cationic lipid, a neutral lipid, a PEG lipid and an active pharmaceutical ingredient, the cationic lipid comprises DOTAP, and the active pharmaceutical ingredient comprises one or more of nucleoside, a nucleoside analogue or a compound with a phosphate group. The lipid nanoparticles are high in stability and bioavailability, and the effect of the lipid nanoparticles is better than that of a drug monomer.

The disclosure features novel lipids and compositions involving the same. Nanoparticle compositions include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Nanoparticle compositions further including therapeutic and / or prophylactics such as RNA are useful in the delivery of therapeutic and / or prophylactics to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.

The disclosure features novel lipids and compositions involving the same. Lipid nanoparticles (e.g., empty LNPs or loaded LNPs) include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Lipid nanoparticles (e.g., empty LNPs or loaded LNPs) further including therapeutic and / or prophylactics such as RNA are useful in the delivery of therapeutic and / or prophylactics to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.

The disclosure features novel lipids and compositions involving the same. Lipid nanoparticles (e.g., empty LNPs or loaded LNPs) include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Lipid nanoparticles (e.g., empty LNPs or loaded LNPs) further including therapeutic and / or prophylactics such as RNA are useful in the delivery of therapeutic and / or prophylactics to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.

The invention relates to the technical field of biological medicines, in particular to a spleen-targeted membrane fusion type delivery carrier as well as a preparation method and application thereof. The delivery carrier comprises a dye and lipid nanoparticles, wherein the lipid nanoparticles comprise an ionizable cationic lipid, an auxiliary lipid and a PEG lipid; the dye is selected from one or more of CyBI7, ICG, Nile Red, IR780, IR820, ICG COOH, Nile Blue, ROX alkynine, ROX amine and BODIPY (Boron Dipyrromethene). The delivery carrier has spleen targeting and membrane fusion characteristics, and the utilization rate and expression efficiency of nucleic acid drugs are remarkably improved.

The present disclosure is based, at least in part, on the discovery that high-purity PEG lipids exhibit superior physical and biological properties, particularly when used in lipid nanoparticle (LNP) formulations. Therefore, the present disclosure provides PEG lipids at a recommended purity, e.g., for use in formulations, such as LNP formulations. The present disclosure also provides LNPs comprising the high-purity PEG lipids, and methods for delivering therapeutic agents to a subject using the same.

Lipid nanoparticles containing a nucleic acid, a cationic lipid, and DOPC, wherein the cationic lipid is at least one selected from the group consisting of CL4H6, Lipid_23, CL4F8-6, YK-009, Lipid_III-45, cKK-E12, C12-200, OF-02, OC2-K3-E10, 306-O12B, 113-O12B, 113-O16B, 306Oi10, CIN-16645, and Lipid_2,2(8,8)_4C_CH3, and the molar ratio of the cationic lipid to the content of the DOPC is 0.2-15.0; and a method for producing the lipid nanoparticles, the method comprising: a step for preparing a lipid solution containing the cationic lipid, DOPC, a sterol, and a PEG lipid; a step for preparing a nucleic acid solution containing a nucleic acid; and a step for mixing the lipid solution and the nucleic acid solution.

The application discloses a nucleic acid lipid nanoparticle preparation, a preparation method thereof and application thereof, and particularly discloses a lipid nanoparticle preparation which comprises a lipid nanoparticle and a freeze-drying protective agent; the lipid nanoparticle comprises a lipid carrier and a nucleic acid; the lipid carrier comprises an ionizable lipid compound or a pharmaceutically acceptable salt thereof, a phospholipid, a sterol and a PEG lipid; the ionizable lipid compound is a compound shown in formula I. The nucleic acid lipid nanoparticle preparation of the application has good lipid nanoparticle integrity, better physical and chemical properties or better biological activity after reconstitution of the freeze-dried preparation.

The invention discloses a lipid composition and application thereof in nucleic acid delivery. The lipid composition can be used for delivery of siRNA through intraarticular administration or subcutaneous administration, and aims to achieve arthritis treatment effects superior to those of existing commercialized proportions of lipid compositions. The lipid composition provided by the invention can be used for delivering nucleic acid drugs, and compared with a marketed LNP formula, the lipid composition has the advantages that the proportion of ionizable cationic lipid is reduced, and the proportion of PEG lipid is increased. When siRNA for treating autoimmune diseases is delivered, the lipid composition is administered through articular cavity injection or subcutaneous injection, especially has a good effect in treatment of collagen-induced rat arthritis (CIA), and remarkably reduces the arthritis score and the foot volume.

The application belongs to the field of biological medicine, and provides a biodegradable amino acid derivative ionizable lipid, a preparation method and application thereof. The lipid structure comprises an amine group head group, an amino acid core connecting part and a hydrophobic lipid tail chain. The prepared lipid nanoparticle formula comprises the above amino acid lipid, a phospholipid, a PEG lipid, an auxiliary lipid and a nucleic acid drug, can safely and efficiently transfect the nucleic acid into cells, and has a wide application prospect in the field of nanometer nucleic acid vaccines, nucleic acid drug preparations and other gene therapies.

To provide improved cationic lipids and lipid nanoparticles for delivery of oligonucleotides.SOLUTION: The lipid nanoparticle of the present invention comprises a cationic lipid and / or a PEG lipid and an mRNA compound comprising an mRNA sequence encoding an antigenic peptide or protein. The invention further relates to the use of said lipid nanoparticle as a vaccine or a drug, in particular for influenza or rabies vaccination.SELECTED DRAWING: Figure 1A

The invention relates to a material for local drug delivery and an application thereof. The invention specifically provides a nano-particle composition. The nano-particle composition comprises cationic lipid, PEG (polyethylene glycol) lipid and structural lipid, wherein the content of the lipid component of the PEG lipid is 1.0-5.5 mol%, or a range between any two of the above values. The nanoparticle compositions of the invention are delivered only at the site of administration.

The present invention provides: a lipid particle which exhibits excellent effects in terms of drug efficacy manifestation, safety (low toxicity), and the like; and a production method therefor. A lipid particle provided by the present invention is, for example, a lipid particle conjugated with an antibody that specifically binds to a cell surface antigen, or an antigen-binding fragment thereof, wherein: the antibody or antigen-binding fragment thereof is covalently bonded to at least a portion of a lipid (reactive polyethylene glycol (PEG) lipid) having a reactive PEG chain contained in lipid components constituting the lipid particle; and the ratio of the reactive PEG lipid, which is not covalently bonded to the antibody or antigen-binding fragment thereof, with respect to all of the lipid components constituting the lipid particle is at most 0.1 mol%.

The application provides an encapsulating object of a composite molecule spike and a preparation method thereof, relates to the technical field of biological medical materials, and the encapsulating object comprises an inner core and an outer layer. The inner core is a molecule spike liposome. Active ingredients of the molecule spike liposome comprise 2-5 wt% of a molecule spike NP, 1-2 wt% of a molecule spike AP and 0.05-0.15 wt% of a plant sphingosine. The outer layer is an extracellular vesicle of long bifidobacterium wrapped outside the inner core. The encapsulating object can effectively improve the problem that the molecule spike is not suitable for common formula systems, significantly enhances the stability of the molecule spike system, and significantly enhances water solubility. A new composite delivery system is constructed by utilizing the natural carrier characteristics of the extracellular vesicle of long bifidobacterium and the biomimetic structure advantages of the molecule spike liposome, and the technical problems of poor solubility, low transdermal absorption rate and insufficient stability of the molecule spike delivery system in the prior art are solved.

The invention provides an LNP-mRNA compound for treating retinitis pigmentosa and a preparation method of the LNP-mRNA compound, and belongs to the field of biological medicines. The present invention relates to a lipid nanoparticle comprising LNP (Lipid Natriuretic Peptide) and mRNA, the mRNA being encapsulated in the lipid nanoparticle or associated with the lipid nanoparticle; the mRNA is IVT mRNA capable of expressing the MERTK protein; the lipid nanoparticles comprise ionized lipid, auxiliary lipid, cholesterol and analogues thereof, and PEG (polyethylene glycol) lipid, the molar ratio of the ionized lipid is 30-68%, the molar ratio of the auxiliary lipid is 8-13%, the molar ratio of the cholesterol or the analogues thereof is 30-43%, the molar ratio of the PEG lipid is 0.5-2%, and the molar ratio of mRNA (messenger ribonucleic acid) to the ionized lipid in the compound is 4-7. The cholesterol and the analogue thereof are preferably sitosterol. According to the formula, the delivery efficiency and the protein expression level of mRNA in intraocular target cells are remarkably improved, and effective intervention and treatment on retinal degenerative diseases are finally realized.