4837results about "Microencapsulation based" patented technology

The invention provides a rapidly metabolized lipid compound, and particularly relates to a compound as shown in 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 nucleic acids. # imgabs0 #

The present disclosure provides compounds according to Formulae I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIII, and XIV for use as a component in a lipid nanoparticle composition for the delivery of biological and / or therapeutic agents. The present disclosure also provides novel, stable lipid nanoparticle compositions comprising one or more biological and / or therapeutic agents, as well as methods of making and delivering lipid nanoparticle compositions.

Ionizable cationic lipids, methods for synthesizing the same, intermediates useful in synthesis of the ionizable cationic lipids, and methods of synthesizing the intermediates are disclosed. The ionizable cationic lipids are useful as a component of lipid nanoparticles (LNP), which in turn can be used for delivering nucleic acids into cells in vivo or ex vivo. LNP compositions are also disclosed, including LNP comprising a functionalized lipid to enable conjugation of a binding moiety, and targeted LNP (tLNP), that is a LNP in which a binding moiety has been conjugated to the functionalized lipid and can serve as a targeting moiety to direct the tLNP to a desired tissue or cell type.

The invention provides a lipid nanoparticle (LNP) compound for efficiently delivering nucleic acid to immune cells, and belongs to a biological medicine technology. According to the present invention, on the basis of the previously researched and developed ionizable cationic lipid 1-126, the Box-Behnken design is adopted to design 13 LNP formulas, and the microfluidic technology is adopted to complete the preparation of the LNP; by detecting the efficiency of LNP transfecting different immune cells and optimizing LNP components, the lipid nanoparticle compound for efficiently delivering mRNA in various immune cells is screened, the compound comprises 40% of cationic lipid 1-126, 16% of DSPC, 1.5% of DMG-PEG2000 and 42.5% of beta-sitosterol, and an efficient delivery system is provided for the fields of vaccine development and gene therapy.

The present disclosure describes improved LNP-based RNA vaccines, nucleobase editing systems, and therapeutics for use in treating and / or immunization against disease. In particular, the disclosure describes improved LNPs, including novel and improved ionizable lipids for making LNPs, that enhance the targeted delivery of LNP-based RNA vaccines and therapeutics based on linear and / or circular mRNAs. The improved LNPs protect linear and / or circular mRNA payloads from degradation and clearance while achieving targeted systemic or local delivery for use as enhanced vaccines and / or therapeutic agents.

The present disclosure provides humanized antibodies and antigen binding domains thereof that bind CD8α and other antibody formats comprising these antigen binding domains, their use as a targeting moiety on lipid nanoparticles (tLNP) to deliver a therapeutic payload (such as a nucleic acid molecule) or other types of payloads. The present disclosure further relates to pharmaceutical compositions comprising the humanized anti-CD8α antibodies and CD8-targeted tLNP encapsulating a payload.

Disclosed are compositions of lipid nanoparticles (LNP) comprising an ionizable cationic lipid, a phospholipid, a sterol, and a PEG-lipid (non-functionalized and optionally functionalized). The functionalized PEG-lipid can be conjugated with a binding moiety to create a targeted LNP (tLNP). The disclosed tLNP preferentially deliver a nucleic acid molecule or other negatively charged payload to cells expressing a cell surface antigen recognized by the binding moiety of the tLNP, and are better tolerated, as compared to LNPs and tLNPs comprising ionizable cationic lipids found in marketed pharmaceuticals comprising LNPs.

Disclosed are compositions of lipid nanoparticles (LNP) comprising an ionizable cationic lipid, a phospholipid, a sterol, and a PEG-lipid (non-functionalized and optionally functionalized). The functionalized PEG-lipid can be conjugated with a binding moiety to create a targeted LNP (tLNP). The disclosed tLNP preferentially deliver a nucleic acid molecule or other negatively charged payload to cells expressing a cell surface antigen recognized by the binding moiety of the tLNP, and are better tolerated, as compared to LNPs and tLNPs comprising ionizable cationic lipids found in marketed pharmaceuticals comprising LNPs.

The invention belongs to the field of biotechnology and medicine, and discloses mRNA (messenger Ribonucleic Acid) for coding luciferase and application thereof. The mRNA for coding the luciferase comprises an ORF sequence for coding the luciferase, and the ORF sequence for coding the luciferase is a nucleotide sequence as shown in one of SEQ ID NO: 10 to SEQ ID NO: 13. The invention provides a brand-new mRNA for coding luciferase, and the mRNA is stable in structure, not easy to degrade, high in translation efficiency, relatively high in protein yield, relatively high in biological availability and safety by reasonably optimizing a nucleic acid sequence of a functional region, can be applied as a reporter gene, and has good potential.

Provided herein are lipids having the Formula I or Formula Ia:and pharmaceutically acceptable salts thereof, wherein R′, R1, R2, R3, R4, R5, R6a, R6b, X1, X2, and n are as defined herein for Formula I and Formula Ia, respectively. Also provided herein are lipid nanoparticle (LNP) compositions comprising lipid having the Formula I or Ia and a capsid-free, non-viral vector (e.g., ceDNA). In one aspect of any of the aspects or embodiments herein, these LNPs can be used to deliver a capsid-free, non-viral DNA vector to a target site of interest (e.g., cell, tissue, organ, and the like).

The invention discloses a CA9-targeted chimeric antigen receptor and application thereof, and belongs to the technical field of biological medicines. The CA9 targeting chimeric antigen receptor provided by the invention comprises a CD8 alpha leading signal peptide, an anti-CA9 single-chain variable fragment, a CD8 alpha hinge, a CD8 transmembrane structural domain and a CD3 zeta intracellular costimulatory signal transduction structural domain. According to the invention, an anti-CA9 single-chain variable fragment is used as an antigen binding structural domain to construct a chimeric antigen receptor (CAR) molecule, the macrophage expressing the anti-CA9CAR can realize specific targeting and phagocytosis killing of CA9 positive kidney cancer cells, and the constructed lipid nanoparticle delivery system can effectively transfer a gene expression vector, so that the gene expression vector can realize effective target site delivery, and the CA9 positive kidney cancer cells can be effectively targeted and killed. The constructed hydrogel-liposome combined drug delivery system has the performance of relieving toxic and side effects, controllable release and hemostasis.

The present disclosure relates to a copolymer and a polymersome for targeted delivery of biomolecules to a living organism. The exemplary copolymer comprises an initiator block, a propagator block, and a linkage connecting the initiator block and the propagator block. The initiator block comprises a glycan head configured to provide a targeted delivery, and the propagator block comprises a functional moiety configured to provide desired properties for the polymersome.

The present disclosure provides bispecific stealth lipid nanoparticle (LNP) compositions engineered to target specific tissues or cell-types, e.g., immune effector cells such as T cells, B cells, natural killer cells, and dendritic cells, to modify the cells with therapeutic nucleic acid encapsulated in the LNP. The present disclosure also provides compositions and methods of making the LNPs and treatment using the same.

The present invention relates to lipids that include novel triazole, and alkyl- and alkene-substituted amine compounds, intermediates in their synthesis, and uses of such triazole, and alkyl- and alkene-substituted amine compounds in, for example, lipid nanoparticle compositions for drug delivery and cancer treatments.

This disclosure provides improved RNA molecules, including mRNA molecules that can be produced by in vitro transcription and are suitable for in vivo transfection using an appropriate delivery vehicle, such as a lipid nanoparticle (LNP) or targeted lipid nanoparticle (tLNP). The improved RNA include particular combinations of 5' untranslated region (UTR) and 3' UTR, particular 3' UTRs, or particular open reading frame sequences. Also provided herein are compositions of the LNP, or tLNP with an antibody as a targeting moiety, such as anti-CD8 antibodies that are used as targeting moiety.

The invention discloses an application of an HERP gene knockout mouse model in obesity and metabolic disorder diseases. The invention finds that compared with a wild type high-fat group, HERP gene knockout can cause phenotypes such as early obesity, more serious obesity degree, increase of fat weight ratio, aggravation of adipose tissue inflammation, dyslipidemia and glucose metabolism disorder of mice during high-fat feeding. And the HERP gene is knocked out, so that the adipocyte differentiation is increased. The HERP gene knockout mouse is more sensitive to nutrition, obesity can occur more quickly during high-fat feeding, symptoms such as fat amplification, fat inflammation and glucose and lipid metabolism disorder are more serious, and the HERP gene knockout mouse can be used for molecular mechanism research and drug screening of obesity, fat tissue and glucose and lipid metabolism disorder. It is further found that cilostazol can significantly relieve mouse obesity and lipid metabolism disorder caused by HERP gene defects, but has no obvious weight losing effect on normal genotype mice, and a new strategy is provided for precise treatment.

The present disclosure relates to a copolymer and a polymersome for targeted delivery of biomolecules to a living organism. The exemplary copolymer comprises an initiator block, a propagator block, and a linkage connecting the initiator block and the propagator block. The initiator block comprises a glycan head configured to provide a targeted delivery, and the propagator block comprises a functional moiety configured to provide desired properties for the polymersome.

The present invention provides a formulation method for encapsulating a negatively charged or hydrophobic target agent by lipid nanoparticles (LNPs). The formulation method comprises impinging an organic phase solution having an ionizable or cationic lipid and an aqueous phase solution. The target agent may be in the organic or aqueous phase solution. The formulation method further comprises self-assembling LNPs, each of which comprises a lipid membrane formed having the ionizable or cationic lipid, whereby the target agent is entrapped by the ionizable or cationic lipid and encapsulated by the LNPs. Also provided is an LNP comprising two or more negatively charged or hydrophobic target agents entrapped by an ionizable or cationic lipid and encapsulated by the LNP. Further provided are the uses of LNPs for intracellular delivery and for stimulating an immune response.

Compounds are provided having the following Structure (I):or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, wherein R1, R1, L1, L2, L2a, L2b, and A are as defined herein. Use of the compounds as a component of lipid nanoparticle formulations for delivery of a therapeutic agent, compositions comprising the compounds and methods for their use and preparation are also provided.

The present disclosure includes ionizable lipids suitable for lipid nanoparticle compositions and pharmaceutical formulations thereof. The lipids have general formula (I).

The present invention provides an ionizable lipid compound having an optimized carbon chain length and an amine head, thereby increasing the delivery efficiency of active molecules, including but not limited to nucleic acids, proteins and small molecule drugs, etc.; the present invention also relates to lipid nanoparticles (lipid nanoparticles, LNPs) comprising the ionizable lipid compound and the active molecule, and a pharmaceutical composition comprising the lipid nanoparticles.

Compositions and methods for delivering nucleic acids (e.g. DNA) to cells are described herein. In some embodiments, the compositions and methods involve the use of lipid nanoparticles comprising cationic lipids, helper lipids, conjugated (PEG) lipids and structural (sterol) lipids wherein the helper lipid has at least one acyl chain bearing an unsaturation which improves in vivo delivery of the nucleic acid pay load.

The present invention generally relates to the field of ionizable (also termed cationic) lipids, and in particular provides a novel type of such lipids as represented by any of the formulae disclosed herein. The present invention further provides methods for making such lipids as well as uses thereof, in particular in the preparation of nanoparticle compositions, more in particular nanoparticle compositions comprising nucleic acids. It further provides vaccine formulations and pharmaceutical formulations comprising nanoparticle compositions based on the ionizable lipids disclosed herein.

The disclosure relates to block copolymer nanoparticles for in vivo therapeutic delivery, and methods therefor. More particularly, the invention relates to polymer nanoparticles, such as reversible addition-fragmentation chain transfer (RAFT) polymer compositions, for encapsulation and for delivery of large nucleic acids.

This disclosure provides improved RNA molecules, including mRNA molecules that can be produced by in vitro transcription and are suitable for in vivo transfection using an appropriate delivery vehicle, such as a lipid nanoparticle (LNP) or targeted lipid nanoparticle (tLNP). The improved RNA include particular combinations of 5′ untranslated region (UTR) and 3′ UTR, particular 3′ UTRs, or particular open reading frame sequences. Also provided herein are compositions of the LNP, or tLNP with an antibody as a targeting moiety, such as anti-CD8 antibodies that are used as targeting moiety.

The purpose of the present invention is to provide a lipid composition capable of delivering a nucleic acid such as RNA to a hematopoietic stem / progenitor cell or a mesenchymal stem cell, and a method for delivering a therapeutic agent to a cell using the lipid composition. The present invention provides a lipid composition comprising (A) a therapeutic agent and (B) a lipid nanoparticle conjugated to a targeting molecule wherein the lipid nanoparticle comprises an ionizable lipid and the targeting molecule specifically binds to a marker of hematopoietic stem / progenitor cells or mesenchymal stem cells.

Compounds are provided having the following Formula (I):or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, wherein G1, G2, R1, R2, R3, L1a, L1b, and L2 are as defined herein. Use of the compounds as a component of lipid nanoparticle formulations for delivery of a therapeutic agent, compositions comprising the compounds and methods for their use and preparation are also provided.

Compounds are provided having the following Formula (I):or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, wherein R1, R2, R3a, R3b, R3c, R3d, L1, L2, and n are as defined herein. Use of the compounds as a component of lipid nanoparticle formulations for delivery of a therapeutic agent, compositions comprising the compounds and methods for their use and preparation are also provided.

The invention relates to the field of prevention and treatment of respiratory diseases, and discloses a preparation method of a human respiratory syncytial virus preventive mRNA vaccine. The main components of the mRNA vaccine comprise mRNA for coding an antigen and lipid nanoparticles. According to the mRNA sequence provided by the invention, an independently researched and developed 5 'UTR / 3' UTR sequence and a codon optimization mode are adopted, and efficient translation of target protein can be realized. According to the mRNA vaccine provided by the invention, RSV F protein is selected as an antigen, and the RSV F protein sequence is optimally designed, so that stable pre-fusion conformation RSV F protein can be expressed, and after a mouse is immunized, the mouse can be induced to generate high-level RSV F protein specific binding antibody titer and neutralizing antibody titer.