3355results about "Microencapsulation based" patented technology

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.

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

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 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.

This disclosure provides methods of increasing in vivo transfection efficiency and pharmacologic activity of T cells, by administering multiple small doses within a compact time period of T cell-targeted lipid nanoparticles encapsulating mRNA encoding an antigen receptor that recognizes an antigen of a cell against which immune activity is to be directed. Also provided are methods of depleting B cells, and methods of treating B cell-mediated diseases and disorders by depleting B cells and achieving immunological reset, entailing administration of immune cell-targeted lipid nanoparticles encapsulating mRNA encoding an antigen receptor recognizing a B cell marker as multiple small doses within a compact time period. The antigen receptor can be a T cell receptor or a chimeric antigen receptor.

Compounds having the structure of Formula (I): or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof; wherein R1, R2, R3, R4, R5, L1, L2, a and z are as defined herein, are disclosed. Use of these 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.

In accordance with the purpose(s) of the present disclosure, as embodied and broadly described herein, the disclosure, in one aspect, relates to lipid nanoparticles for use as drug delivery agents. The lipid nanoparticles are composed of lipopeptide conjugates, where a peptide is bonded to a lipid. The lipid nanoparticles described herein represent a new approach in drug delivery, addressing critical challenges in balancing biodegradability, biocompatibility, and organspecific targeting. The lipid nanoparticles can selectively target and deliver bioactive agents to specific tissues in a subject by modifying specific amino acids and ratios thereof in the peptide of the lipopeptide conjugate.

The present disclosure provides bispecific stealth lipid nanoparticle (LNP) compositions engineered to target specific tissues or cell-types, e.g., hematopoietic stem 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 disclosure provides conjugates comprising a targeting moiety a lipid nanoparticle (LNP) encapsulating a therapeutic agent (e.g., payload) for delivery to immune cells. The conjugates can be delivered to immune cells ex vivo or formulated in a pharmaceutical composition and can be directly administered to a subject in need of (i.e., via in vivo administration).

The disclosure provides, for example, double stranded DNA (dsDNA) molecules comprising one or more chemically modified nucleobases. In some embodiments, the dsDNA molecule is circular and comprises a first strand and a second strand, wherein the first strand comprises one or more chemically modified nucleobases, and the second strand is free of chemically modified nucleobases. In some embodiments, the dsDNA molecule comprises a promoter sequence and an effector sequence that encodes an effector.

The instant disclosure relates to lipid particles that harbor cationic lipids, the particles found to be capable of delivering associated cargoes - particularly nucleic acid cargoes when formulated as nucleic acid-lipid particles - intracellularly to skin tissue cells when administered topically to a subject. The instant disclosure provides compositions comprising such lipid particles, optionally in association with a therapeutic agent (e.g., a therapeutic mRNA and / or nucleic acid controller system), as well as methods and kits for delivering a lipid particle-associated therapeutic agent and / or for treating or preventing a disease or disorder, e.g., a skin disease or disorder, in a subject, using one or more lipid particle compositions provided herein.

Provided herein are circular RNA constructs comprising an IRES, and at least one expression sequence encoding binding molecule, compositions thereof, and methods of treating autoimmune disease. In particular, circular RNA comprising an IRES and a CD19 binder or a BCMA binder are provided, optionally formulated with a delivery vehicle. Precursor polynucleotides comprising an IRES, and at least one expression sequence encoding a CAR construct are also described herein.

Provided are variant Cas12f4 polypeptides, fusion proteins containing variant Cas12f4 polypeptides, nucleic acids encoding variant Cas12f4 polypeptides and fusion proteins, compositions and methods related to those variant Cas12f4 polypeptides and fusion proteins, and modified host cells comprising the variant Cas12f4 polypeptides and / or encoding nucleic acids. The variant Cas12f4 polypeptides disclosed herein exhibit improved functionality, stability, and / or other desirable properties and may be used in combination with guide Cas12f4 RNAs that can be used in a variety of applications ex vivo, in vitro, and in vivo.

Certain embodiments of the invention provide a cationic lipid of formula (I):wherein R1, R2, R3 and R4 are defined as described herein, as well as methods of making these lipids. Certain embodiments of the invention also provide nucleic acid-lipid particles comprising a cationic lipid of formula (I), methods of making the lipid particles, and methods of delivering and / or administering the lipid particles.

The present disclosure provides novel polymer-conjugated lipids conjugated to a polyglycerol or a polyglycerol derivative. The present disclosure also provides lipid nanoparticles (LNPs) formulation using the polymer-conjugated lipids and methods of treating a disease by administering the LNP formulations, including multiple doses of the LNP formulations.

Lipid nanoparticles comprising ionizable lipids, helper lipids, neutral lipids, structural PEG-lipids, and anchor PEG-lipids are provided herein, together with targeted lipid nanoparticle compositions, and uses thereof. Methods of administering targeted lipid nanoparticles and targeted lipid nanoparticle compositions for the delivery of biologically active agents, are also provided. Such compositions and methods can be used, for example, to deliver a cargo (e.g., a mRNA cargo), to a cell population of interest.

In some aspects, the present disclosure provides compositions of lipid nanoparticles useful for the delivery of large RNAs including mRNAs. These compositions may include a cationic ionizable lipid, a phospholipid, a PEGylated lipid, and a steroid including using less of a cationic ionizable lipid than compositions with shorter nucleic acids. These compositions may be used to treat a disease or disorder for which the delivery of an mRNA is therapeutically effective.

Provided are methods for delivering lipid nanoparticles (LNPs) to a lung cell of a subject suffering from or at risk for primary ciliary dyskinesia (PCD), wherein the method comprises nebulizing a liquid pharmaceutical composition to generate an aerosolized pharmaceutical composition, and administering the aerosolized pharmaceutical composition to the subject.