122 results about "Peg lipid" patented technology

Targeting lipid nanoparticles for nucleic acid delivery, In one embodiment, the targeting lipid nanoparticle includes an ionizable lipid, a cholesterol or cholesterol derivative, a helper lipid, a PEG lipid, a targeting lipid, and a nucleic acid. In other embodiments, the targeting lipid nanoparticle including an ionizable lipid, a cationic lipid, a cholesterol or cholesterol derivative, a helper lipid, a PEG lipid, a targeting lipid; and a nucleic acid. In other embodiments, the targeting lipid nanoparticle including an ionizable lipid, a cholesterol or cholesterol derivative, a helper lipid, a PEG lipid, a functionalized lipid; and a nucleic acid. In other embodiments, the targeting lipid nanoparticle including an ionizable lipid, a cationic lipid, a cholesterol or cholesterol derivative, a helper lipid, a PEG lipid, a functionalized lipid; and a nucleic acid. Also provided are kits for preparing targeting lipid nanoparticles and functionalized lipid nanoparticles for nucleic acid delivery.

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.

Targeting liposomes for protein degrader delivery. In one embodiments, the targeting liposome including a phospholipid, a cholesterol or cholesterol derivative, a PEG lipid, a targeting lipid; and a protein degrader. In other embodiments, the targeting liposome including a phospholipid, a cholesterol or cholesterol derivative, a PEG lipid, a targeting lipid; and a protein degrader- ligase complex. Also provided are kits for preparing targeting liposomes for protein degrader and / or protein degrader-ligase complexes. Also provided are methods for preparing such targeting liposomes.

The present application relates to a nanoparticle comprising a lipid, a polymer and an immunosuppressive agent, wherein the lipid comprises an anionic lipid and / or a PEGylated lipid. Furthermore, the invention also relates to a preparation method of the nanoparticles, a pharmaceutical composition containing the nanoparticles, and application of the nanoparticles and / or the pharmaceutical composition in inducing immune tolerance.

The invention discloses a PEG lipid compound and application thereof. The structure of the PEG lipid compound is shown as a formula (I), and x is a positive integer selected from 11-17. The PEG lipid compound provided by the invention has good biocompatibility and excellent in-vivo mRNA delivery efficiency. The PEG lipid compound disclosed by the invention is high in synthesis efficiency and low in cost, and is convenient for large-scale production and commercial application. According to the present invention, the delivery effect of the PEG lipid compound corresponding to the LNP formula exceeds the delivery effect of the commercialized ionizable lipid SM-102 and the commercialized PEG lipid DMG-PEG2000; # imgabs0 #

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.

Novel ionizable lipids, compositions, and methods of using the novel lipids and compositions are disclosed. Lipid nanoparticle compositions include novel lipids as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Lipid nanoparticle compositions further including biologically active agents such as mRNA are useful in the delivery of therapeutics, diagnostics and / or prophylactics to cells or organs.

The invention discloses a circRNA nano delivery system capable of reversing nucleus pulposus progenitor cell senescence and a preparation method and application of the circRNA nano delivery system. The circRNA nano delivery system comprises: a) Klotho circRNA, and b) a liposome, and the liposome comprises a vascular peptide vasculotide, an ionizable lipid molecule, a phospholipid, a PEG lipid, and a steroid. The invention also provides application of the circRNA nano delivery system capable of reversing nucleus pulposus progenitor cell senescence in preparation of drugs for treating intervertebral disc degeneration. The invention provides liposome particles (Vas-Klotho-LNP) which have targeted NPPCs and wrap circRNA, Klotho circRNA is efficiently introduced into the NPPCs through Tie2 agonist peptide, so that rejuvenation of the NPPCs is promoted, ECM synthesis is promoted, and regeneration and repair of intervertebral discs are synergistically promoted in vivo and in vitro.

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 invention discloses a double-selenium lipid nanoparticle as well as a preparation method and application thereof. According to the nanoparticle, a skeleton is composed of cationic lipid, neutral phospholipid, cholesterol and functionalized PEG lipid, meanwhile, mRNA and a TLR agonist for coding therapeutic protein are carried, and the nanoparticle is synthesized through an ethanol injection method; the nanoparticle has both active targeting and strong transfection capabilities, the lipid nanoparticle is actively targeted to a tumor microenvironment and is taken by tumor cells by using biotin modified PEG lipid, and rapid'inclusion-lysosome 'escape is realized in the tumor cells by using trifluorogroup modified PEG lipid. Meanwhile, the nanoparticles are degraded in a glutathione / hydrogen peroxide dual-mode, so that the entrapped medicine is quickly and effectively released; the drug delivery system provided by the invention is simple in synthesis method, high in gene transfection efficiency and good in biological safety, and has potential value in anti-tumor research and clinical application.

The present invention provides a lipid nanoparticle including an ionic lipid represented by the following formula (1) wherein the symbols are as defined in the specification and an activated PEG lipid-bonded ligand having cell directivity.

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.

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 present disclosure provides compositions that exhibit preferential targeting or delivery of nucleic acid compositions to specific organs. In some embodiments, the compositions comprise steroids or sterols, ionizable cationic lipids, phospholipids, PEG lipids, and permanent cationic lipids, which can be used to deliver nucleic acids. The invention also provides the use of the composition in the preparation of a medicament for targeted delivery of a therapeutic agent to an organ or cells in an organ.

The present disclosure in part provides compounds (i.e., PEG lipids) which are useful in pharmaceutical compositions, cosmetic compositions, and drug delivery systems, e.g. for use in lipid nanoparticle (LNP) formulations. The present disclosure also provides LNP formulations comprising PEG lipids described herein, and methods of using the same. For example, the LNPs provided herein are useful for the delivery of an agent (e.g., therapeutic agent) to a subject. The PEG lipids and LNPs provided herein, in certain embodiments, exhibit increased PEG shedding compared to existing PEG lipids and LNP formulations.

The present disclosure provides PEG lipids and transfer vehicle compositions including the same. Incorporation of the PEG lipids of this disclosure into a transfer vehicle can provide for one or more desirable properties, including low immune response and / or immunogenicity, fast-shedding of the PEG lipid from the transfer vehicle, and / or degradability of the PEG lipid, e.g., via ester hydrolysis or cleavage.

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 disclosure features novel lipids and compositions involving the same. Lipid nanoparticles include a novel ionizable lipid as well as additional lipids such as cationic lipids, phospholipids, structural lipids, and PEG lipids. Lipid nanoparticles 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.

The present disclosure provides compositions which facilitate preferential targeting or delivery of a therapeutic agent to a particular organ, cell, or tissue. The presently disclosed compositions comprise lipid nanoparticles formed from a covalent-bond forming lipid, a cationic lipid, and, in some embodiments, a steroid or sterol, a phospholipid, and a PEG lipid.

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.

Provided are lipid nanoparticles containing (A) an ionic lipid represented by formula (1) (wherein the symbols in formula (1) are as defined in the description), (B) vitamin E and / or a derivative thereof, (C) a phospholipid, (D) cholesterol, and (E) a PEG lipid. # imgabs0 #

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 present disclosure provides compositions that show preferential targeting or delivery of nucleic acid compositions to specific organs. In some embodiments, the compositions comprise steroids or sterols, ionizable cationic lipids, phospholipids, PEG lipids, and permanent cationic lipids that can be used to deliver nucleic acids.

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 lipid nanoparticles, which can encapsulate any nucleic acid with high efficiency and with ease. A method for producing nucleic acid-encapsulated lipid nanoparticles, including the following steps: a) a step of preparing a suspension of lipid nanoparticles not containing a nucleic acid, by mixing an alcohol solution containing ionic lipid, sterol and PEG lipid with an acidic buffer having a buffering action at pH 1 to 6.5, and b) a step of mixing, without lyophilization, the suspension of the lipid nanoparticles obtained in step a with an aqueous solution containing a nucleic acid and optionally containing 0 to 25 v / v% alcohol, and optionally incubating the mixture at 0 to 95°C for 0 to 60 min to obtain nucleic acid-encapsulated lipid nanoparticles.