72 results about "Peg lipid" patented technology

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 discloses an antibody-modified lipid nanoparticle, a preparation method thereof and application of the antibody-modified lipid nanoparticle as a targeting carrier. The invention provides lipid nanoparticles coupled with an antibody and loaded with nucleic acid. The lipid nanoparticles are characterized in that raw materials of the lipid nanoparticles consist of ionizable lipid, phospholipid, steroidal lipid, PEG lipid and PEG-Mal lipid, the PEG lipid is C16-PEG2k, and the PEG-Mal lipid is C16-PEG2k-Mal, and the PEG-Mal lipid is C16-PEG2k-Mal. The method aims at the key scientific problems of low delivery efficiency, insufficient targeting and the like in the field of in-vivo hematopoietic stem / progenitor cell gene therapy at present. The invention develops a lipid nanoparticle delivery system based on antibody modification, provides a modular antibody targeted delivery platform with high universality, and shows huge clinical transformation potential.

The invention provides an amino acid skeleton ionizable lipid as well as a preparation method and application thereof, the amino acid skeleton ionizable lipid is modified by taking amino acid as a core, has more ester groups and peptide bonds, and can be quickly hydrolyzed by enzyme after RNA is effectively released in vivo; the transfection body is provided with four tail structures, the cross sectional area of the lipid tail can be increased, drugs such as RNA are helped to escape from an endosome, and then the transfection effect is enhanced; the charge capable of ionizing the lipid is electrically neutral under physiological conditions, so that the cytotoxicity caused by excessive positive charges is reduced, the stability of the lipid nanoparticles is further improved, the cycle time of the loaded nucleic acid medicine is prolonged, and the pharmacokinetic characteristics are improved. The LNP prepared from the ionizable lipid, auxiliary phospholipid, cholesterol and PEG lipid provided by the invention has more excellent nucleic acid carrier performance, and can effectively deliver nucleic acid drugs such as siRNA, mRNA, pDNA and the like into cells to play a role.

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 invention relates to a lipid composition, which comprises a polymer lipid, and the polymer lipid is a compound with a structure as shown in a formula (I), or a pharmaceutically acceptable salt, an isotope variant, a tautomer or a stereoisomer thereof. The invention also provides a nanoparticle composition and a pharmaceutical composition comprising the lipid composition, and an application of the lipid composition in delivery of a load. The polymer lipid compound in the lipid composition can replace PEG lipid and has the advantages of biocompatibility, easiness in decomposition in vivo and no toxicity, so that a novel lipid delivery system is obtained.

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 a polymer lipid compound, in particular to a compound as shown in a formula (I), or pharmaceutically acceptable salt, isotope variant, tautomer or stereoisomer thereof. The invention also provides nanoparticle pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions thereof in delivery of loads. The polymer lipid compound can replace PEG lipid and has the advantages of biocompatibility, easiness in decomposition in vivo and no toxicity, so that a novel lipid delivery system is obtained.

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 present application relates to the technical field of nucleic acid drug preparation, and discloses a lipid nanoparticle based on asiatic acid and a preparation method and application thereof, the lipid nanoparticle is composed of ionizable cationic lipids, structural lipids, neutral lipids, PEG lipids and asiatic acid with a molar ratio of 10-85:20-60:1-30:0.1-10:0.1-50, and is used as a delivery carrier of nucleic acid drugs for delivering nucleic acid drugs. The present application innovatively uses natural product asiatic acid to partially replace the structural lipids (such as cholesterol) in the traditional LNP formula, significantly optimizes the micro morphology, and greatly enhances the transfection and expression efficiency of mRNA in vitro and in vivo. The mRNA vaccine based on the carrier can induce the body to produce high-titer specific antibodies and significantly enhance the cytotoxic T lymphocyte (CTL) killing activity. The LNP system performs outstandingly in the field of tumor immunoprevention and treatment, and shows superior conversion application potential and broad market prospects.

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 application provides new cationic lipid compounds and a composition containing the compounds. A nanoparticle composition contains new cationic lipid compounds and other lipids, such as phospholipids, structural lipids and PEG lipids. Additionally, the nanoparticle composition of the present application can be used to deliver a therapeutic agent and / or a prophylactic agent to mammalian cells or organs to, for example, regulate polypeptide, protein or gene expression.

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

The present invention provides a polyamino acid polymer material having the following chemical formula: R1 is a hydrophilic amino acid repeating segment or a combination of hydrophilic and hydrophobic amino acid repeating segments; R2 is a linker for connecting the hydrophilic group and the hydrophobic group; R3 is a transitional moiety for reinforcing the connection of the hydrophobic group and preventing substitution reactions; the six-membered ring in the formula is selected from at least one of a benzene ring, cyclohexane, heterocyclohexane, cyclohexene, heterocyclohexene, pyridine, or pyran; and n and m are natural numbers. The present invention uses a polyamino acid polymer material instead of PEG lipids, effectively avoiding the effects of pre-existing anti-PEG antibodies, exhibiting good biodegradability, effectively improving the physical dispersion stability of nanoparticles, and increasing the long-term circulation of nanoparticles in the body. The four-component formula of traditional lipid nanoparticles can be reduced to a three-component formula, resulting in excellent stability of the prepared liposomes and nanocrystal preparations over a certain period of time while retaining the inherent drug-loading advantages of liposomes.

The disclosure features amino lipids and compositions involving the same. Nanoparticle compositions include an amino lipid as well as additional lipids such as phospholipids, structural lipids, PEG lipids, or a combination thereof. Nanoparticle compositions further including therapeutic and / or prophylactic agents such as RNA are useful in the delivery of therapeutic and / or prophylactic agents to mammalian cells or organs to, for example, regulate 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 invention provides a method for producing nucleic acid-encapsulated lipid nanoparticles, the method comprising the following steps (a) and (b): a step (a) for preparing a suspension of nucleic acid-encapsulated lipid nanoparticles by mixing an alcoholic solution containing an ionic lipid having a tertiary amino group, a sterol, and a PEG lipid with a citric acid buffer solution having a pH of 3-6.5 in which a nucleic acid is dispersed; and a step (b) in which a suspension of nucleic acid-encapsulated lipid nanoparticles is subjected to ultrafiltration concentration and diluted with a Tris buffer solution having a pH of 5.2-9.0, thereby replacing the dispersion medium of the suspension with the Tris buffer solution.

The invention relates to the technical field of nucleic acid medicine preparations, and discloses lipid nanoparticles based on asiatic acid and a preparation method and application thereof.The lipid nanoparticles are composed of ionizable cationic lipid, structural lipid, neutral lipid, PEG lipid and asiatic acid according to the molar ratio of (10-85): (20-60): (1-30): (0.1-10): (0.1-50) and serve as delivery carriers of nucleic acid medicine. For delivery of nucleic acid drugs. According to the invention, a natural product asiatic acid is creatively adopted to partially replace a structural lipid (such as cholesterol) in a traditional LNP formula, and the micromorphology of the LNP is obviously optimized, so that the in-vivo and in-vitro transfection and expression efficiency of mRNA is greatly enhanced. The mRNA vaccine constructed based on the vector can induce an organism to generate a high-titer specific antibody, and the killing activity of cytotoxic T lymphocytes (CTL) is remarkably enhanced. The LNP system has outstanding performance in the field of tumor immunoprophylaxis and treatment, and shows excellent transformation application potential and wide market prospect.

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.

Novel ionizable lipid compounds, compositions comprising such ionizable lipid compounds, and related methods of use thereof are disclosed. Nanoparticle compositions comprise novel lipids and additional lipids, such as phospholipids, structural lipids, and PEG lipids. The nanoparticle composition also comprises a bioactive agent, such as siRNA or mRNA, which can be used to deliver the bioactive agent to an individual in need thereof.

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.