106 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 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 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 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.

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.

Lipid nanoparticles, compositions comprising lipid nanoparticles, and methods of making and using lipid nanoparticles. In various examples, a lipid nanoparticle: ionizable cationic amino lipid(s); PEG-lipid(s); phospholipid(s); and sterol(s); or a combination component comprising two or more groups having the functionality of two the aforementioned lipid components, which replaces those two aforementioned lipid components; and optionally, one or more cationic lipid component(s). In various examples, the lipid nanoparticle comprises one or more peptide(s), functionalized peptide(s), or the like, or any combination thereof, one or more of which may be therapeutic. In various examples, a composition, which may be a pharmaceutical composition, comprises a plurality of the lipid nanoparticles. In various examples, the lipid nanoparticles are used in method of delivering peptide(s), functionalized peptide(s), or the like, or any combination thereof. In various examples, the lipid nanoparticles are administered to an individual, which may be in need of treatment.

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 invention relates to a pH responsive PEG lipid compound based on a benzimide bond and application of the pH responsive PEG lipid compound. The invention provides a pH responsive PEG (Polyethylene Glycol) lipid compound Ben-PEG2000 containing a benzimide bond. The chemical formula of the pH responsive PEG lipid compound Ben-PEG2000 is shown as a formula (I). The lipid nanoparticle containing the pH responsive PEG lipid compound Ben-PEG2000 provided by the invention has a pH responsive characteristic, can promote endosome escape and transfection efficiency of mRNA loaded in the lipid nanoparticle in a pH responsive manner in an endosome weak acid environment, has extremely high safety, and has a wider clinical application value. # imgabs0 # (I).

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.