9379results about "Gene therapy" patented technology

The invention provides an UTR (Untranslated Region) element H2202 P1-G as well as a construction method and application thereof, and relates to the technical field of mRNA (messenger ribonucleic acid). According to the present invention, the ribosome load prediction and the secondary structure optimization are performed on the natural 5 'UTR of the HIV TAT 202 gene through the BaidleHelix platform, and the obtained HTAT 202 P1 sequence avoids the inhibitory hairpin structure so as to significantly improve the luciferase expression quantity compared to the natural UTR; an ncRNA sequence without a secondary structure is introduced on the basis of the HTAT 202 P1, translation inhibition of a 5 'cap region is further relieved, and the protein expression quantity of the constructed H2202 P1-G mutant (the DNA sequence of the H2202 P1-G is as shown in SEQ NO 1, and the RNA sequence is as shown in SEQ NO 2) is further improved.

The invention provides an UTR element NHP1 as well as a construction method and application thereof, and relates to the technical field of mRNA. A 5 'UTR with a good expression effect is designed by integrating dominant sequences of a human high-expression gene and a pathogen natural UTR, a chimeric structure NHP1 with high ribosome load is predicted through a calculation model, a DNA sequence of the NHP1 is as shown in SEQ NO 1, and an RNA sequence of the NHP1 is as shown in SEQ NO 2; an EGFP report system is adopted on the DNA level to rapidly screen UTR; the translation efficiency is quantitatively evaluated on the RNA level through luciferase mRNA (N1-methyl pseudouridine modification); and the particle size is controlled by a microfluidic technology, so that the optimized UTR-mRNA is efficiently expressed after being delivered.

The invention provides a production strain of an antibiotic-free plasmid, the production strain is a gene editing strain of a PIR strain and is named as PIR1-WN:: 0636 or PIR1-PR: 0636, the production strain contains a nucleotide sequence for coding toxin protein and the antibiotic-free plasmid, and the antibiotic-free plasmid contains a nucleotide sequence for coding antitoxin protein; and preferably, the replicon DNA element of the nonreactive plasmid is R6K-gamma. The toxin protein gene of the production strain disclosed by the invention can be stably passaged, has lethality after being induced and can be used for plasmid screening; according to the invention, the positive rate of transforming the nonreactive plasmid into the PIR1-WN:: 0636 strain is more than 80%, and stable production of the plasmid with a high superhelix ratio can be realized.

The present invention relates to the field of lentiviral delivery. Specifically provided are a mutated vesicular virus envelope protein and the use thereof in lentiviral vector packaging.

The invention provides a UTR (Untranslated Region) sequence for improving mRNA (Messenger Ribonucleic Acid) stability and translation efficiency and application of the UTR sequence, and particularly provides an mRNA molecule which comprises a coding region for coding polypeptide or protein and a fragment thereof, a 5 'UTR sequence positioned at the upstream of the coding region and / or a 3' UTR sequence positioned at the downstream of the coding region, the 5 'UTR sequence is a nucleotide sequence as shown in SEQ ID NO: 1, and the 3' UTR sequence is a nucleotide sequence as shown in SEQ ID NO: 2; and / or, the 5 'UTR sequence is a nucleotide sequence as shown in SEQ ID NO: 3, and the 3' UTR sequence is a nucleotide sequence as shown in SEQ ID NO: 4. According to the present invention, the mRNA stability and the translation efficiency are improved through the new and optimized UTR sequence, and the UTR sequence can be used as the element for enhancing the RNA expression efficiency in the nucleic acid treatment drug or the mRNA vaccine so as to provide more and better choices for the mRNA therapy.

The present disclosure relates to compositions and methods for reducing expression of MYC gene in a cell. In some embodiments, an expression repressor comprises a targeting moiety that binds a MYC promoter, anchor sequence, or super-enhancer. In some embodiments, the expression repressor comprises an effector moiety that represses transcription or methylates DNA. Systems comprising two expression repressors are also disclosed. The compositions can be used, for example, to treat cancers such as HCC.

A pharmaceutical composition comprising a first RNAi agent and a second RNAi agent, the first RNAi agent comprising one or more first and / or one or more first siRNA conjugates capable of inhibiting APOC3 mRNA; a second RNAi agent comprising one or more second siRNAs and / or one or more second siRNA conjugates capable of inhibiting PCSK9 mRNA; the weight ratio of the first RNAi agent to the second RNAi agent in the pharmaceutical composition is (10: 1)-(1: 10) based on the total amount of the siRNA and the siRNA group. The pharmaceutical composition and the treatment method can effectively treat and / or prevent diseases or symptoms related to hyperlipidemia.

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 invention provides a hypoglycemic peptide which is prepared by taking bovine whey protein as a raw material and is stable in gastrointestinal digestion and absorption. In an in-vitro cell experiment, the peptide fragment can improve the uptake of insulin-resistant HepG2 hepatocytes and synthesize glycogen by using glucose, can promote intestinal endocrine cells NCI-H716 to secrete GLP-1, has a certain synergistic effect, and can further play the effects of promoting GLP-1 secretion and activating a GLP-1 receptor through combined use. An insulin resistance mouse model is constructed by utilizing high-fat diet, and the peptide fragment is adopted for intervention, so that the hypoglycemic peptide is further proved to have obvious effects on losing weight, reducing lipid accumulation and assisting in reducing blood fat, and meanwhile, the hypoglycemic peptide can be used for improving insulin resistance related symptoms. The milk peptide provided by the invention has gastrointestinal digestion stability and hypoglycemic activity, can be used as a functional milk base material for developing food, medicines or health care products with the effect of regulating blood sugar, and is wide in application prospect.

The invention relates to a ligand-effector moiety provided with at least one saponin and antibody-effector moiety provided with at least one saponin. An aspect of the invention is a composition comprising the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin of the invention. The invention also relates to an antibody-drug conjugate comprising covalently linked saponin and to an antibody-oligonucleotide conjugate comprising covalently linked saponin. An aspect of the invention relates to a pharmaceutical composition comprising the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin of the invention, and optionally further comprising a pharmaceutically acceptable excipient. The invention also relates to the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin, for use as a medicament. The invention also relates to the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin of the invention for use in the treatment or prophylaxis of a cancer.

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 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.

Disclosed herein are an engineered immune cell with CD7 gene knock-out and use thereof. According to the present invention, an sgRNA specifically targeting CD7 gene is designed and synthesized, which can accurately target CD7 gene to achieve gene knock-out with high knock-out efficiency. The provided sgRNA can be used for preparing a CD7-targeting engineered immune cell, and can be further used for preparing a CD7-targeting universal CAR-T cell

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.

A printed circuit board according to an embodiment comprises: an insulating layer; a circuit pattern disposed on the upper surface of the insulating layer; a support layer which is disposed on the upper surface of the insulating layer to expose the upper surface of the circuit pattern and is in contact with the sides of the circuit pattern; and a protective layer disposed on the upper surfaces of the support layer and the circuit pattern, wherein the upper region of the insulating layer comprises a first region and a second region, and the protective layer comprises an open region exposing the upper surfaces of the support layer and the circuit pattern that are disposed in the first region, and the support layer comprises a first upper surface positioned at the highest level among the upper surfaces of the support layer and a second upper surface positioned at the lowest level among the upper surfaces of the support layer, the second upper surface being lower than the first upper surface, and the protective layer comprises a first portion which contacts the upper surface of the circuit pattern of the first region and a second portion which contacts the upper surface of the support layer of the first region, and the second portion of the protective layer contacts the second upper surface of the support layer and includes a first lower surface which is lower than the upper surface of the circuit pattern.

The invention discloses an engineered bionic nucleic acid nano-vesicle as well as a preparation method and application thereof, relates to the technical field of nano biomedicine, and aims at solving the problems that in-vivo targeting efficiency and immunogenicity of a traditional cationic lipid nano-carrier are limited due to deletion and cleavage obstacles of GSDMD expression in tumor cells. The technical key point of the invention is as follows: the engineered bionic nucleic acid nano-vesicle is provided and is prepared by wrapping a cationic lipid nucleic acid drug with an exosome derived from engineered macrophages; wherein the exosome from the engineered macrophage is the exosome from the macrophage with high expression of PD1, which is as shown in SEQ. ID. NO.1. The exosome from the engineered macrophage is the exosome from the macrophage with high expression of PD1; the lipid nucleic acid medicine is prepared by loading GSDMD-N mRNA (messenger Ribonucleic Acid) shown on the basis of SEQ.ID.NO.2 on a cationic liposome. The engineered bionic nucleic acid nano-vesicle is used for preparing an oral squamous cell carcinoma diagnostic kit and a therapeutic drug.

The present invention relates to a nucleic acid molecule for inhibiting FXI gene expression through RNAi, and more particularly, to a nucleic acid molecule for inhibiting FXI gene expression through RNAi, the nucleic acid molecule comprises a sense sequence and an antisense sequence which are complementary to each other or is composed of a sense sequence and an antisense sequence which are complementary to each other, and the FXI inhibition rate of the nucleic acid molecule is significantly superior to that of other small nucleic acid molecules for inhibiting FXI expression through RNAi.

The invention discloses a lipid compound capable of being used for gene delivery, a preparation method of the lipid compound and application of the lipid compound in gene delivery. Also disclosed herein is a lipid nanoparticle comprising the lipid compound, a gene delivery composition comprising the lipid compound or the lipid nanoparticle. The lipid compounds, lipid nanoparticles and delivery systems herein enable efficient complexation, protection, intracellular and targeted delivery and release of biomolecules, such as oligonucleotides and nucleic acids, in vitro and in vivo tissues and organs.

To provide a new composition for increasing expression of the Klotho gene and an application thereof.SOLUTION: The present disclosure provides, in one aspect, the following invention: a composition for enhancing expression of the human Klotho / KL gene, the composition comprising at least a portion of a protein belonging to the TNF superfamily or a nucleic acid encoding at least a portion of the protein.SELECTED DRAWING: None

The invention relates to an application of an intervention SNRK-MTA1 signal channel axis in preparation of a non-small cell lung cancer targeted therapy drug. The nucleotide sequences of the mRNA of the SNRK gene and the mRNA of the MTA1 gene are respectively as shown in SEQ ID NO.1-2. The invention innovatively provides a strategy for treating the non-small cell lung cancer through double-target combined intervention. According to the strategy, SNRK gene expression is improved through exogenous gene overexpression plasmids, and meanwhile MTA1 gene expression is silenced through the siRNA technology. In a non-small cell lung cancer model, the strategy of combined application of the SNRK-OE plasmid and siMTA1 can specifically up-regulate the SNRK mRNA level and knock down the MTA1 mRNA level at the same time, and the combined strategy shows a better anti-tumor effect than single intervention, and can more effectively inhibit the growth and migration of tumor cells. Based on the discovery, the SNRK-MTA1 signal pathway axis can be developed into a novel therapeutic target for non-small cell lung cancer, and is used for designing a drug combination scheme or a composite targeted drug.

The present disclosure provides materials and methods for delivery of a transgene to target cells. The regulatory elements, transgenes, and expression vectors are useful in, e.g., expressing a transgene in CNS cells that results in an improvement in at least one symptom related to a neurological disease or disorder, including epilepsy disorders, such as refractory epilepsy.

The present invention provides a novel therapeutic drug for treating a Prom1-associated retinal disease. Specifically, the present invention provides an optimized Prom1 gene expression cassette, an rAAV viral vector, and a gene therapy drug. The drug of the present invention can specifically express the PROM1 protein in the retinal photoreceptor layer, and is suitable for the clinical treatment of a retinal disease associated with Prom1 gene mutation.

The present disclosure provides codon optimized GBA1 polynucleotides encoding a GCase protein, wherein a portion of the coding sequence deviates from the wild type. The disclosure also provides expression constructs, vectors, viral particles or compositions containing the disclosed polynucleotides. In addition, methods and uses of these polynucleotides, expression constructs, vectors, viral particles or compositions are also provided, including the treatment of diseases or conditions associated with GCase deficiency.

Among other things, the present disclosure provides oligonucleotides, compositions and methods thereof that are useful for adenosine modification. In some embodiments, the present disclosure provides methods for treating various conditions, disorders or diseases that can benefit from adenosine modification.

The present invention is directed to lipid nanoparticles using cationic cholesterol for topical delivery for nucleic acid delivery, and when administered locally, side effects caused by systemic drug delivery can be minimized and protein expression can be confined to the site of administration. In addition, the duration of protein expression at the site of administration can be increased, and thus the lipid nanoparticles can be useful in the technical field related to nucleic acid therapeutics.

Provided herein are engineered nucleic acids (e.g., expression vectors, including viral vectors, such as lentiviral vectors, adenoviral vectors, AAV vectors, herpes viral vectors, and retroviral vectors) that encode OCT4; KLF4; SOX2; or any combination thereof that are useful, for example, in inducing cellular reprogramming, tissue repair, tissue regeneration, organ regeneration, reversing aging, or any combination thereof in the central nervous system or ex vivo. Also provided herein are recombinant viruses (e.g., lentiviruses, alphaviruses, vaccinia viruses, adenoviruses, herpes viruses, retroviruses, or AAVs) comprising the engineered nucleic acids (e.g., engineered nucleic acids), engineered cells, compositions comprising the engineered nucleic acids, the recombinant viruses, engineered cells, engineered proteins, chemical agents that are capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, an engineered protein selected from the group consisting of OCT4; KLF4; SOX2; or any combination thereof, an antibody capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, and methods of treating a disease (e.g., a neurological disease), preventing a disease (e.g., neurological disease), regulating (e.g., inducing or inducing and then stopping) cellular reprogramming, regulating tissue repair, regulating tissue regeneration, or any combination thereof.

Disclosed herein include methods, compositions, and kits suitable for use in e.g., nucleic acid delivery. Provided are compositions (e.g., nucleic acid compositions) comprising polynucleotide(s) encoding a fusion protein, a dimerization fusion protein, a soluble RBP, an adapter fusion protein, and / or a cell fusion protein. The compositions also comprise one or more polynucleotides comprising one or more RNA cargo molecules. The fusion protein, dimerization fusion protein, and / or adapter fusion protein can comprise an endosomal sorting complex required for transport (ESCRT)-recruiting domain (ERD). Recruitment of one or more ESCRT proteins results in secretion of enveloped nanoparticles (ENPs) from a cell in which at least one of a fusion protein, a dimerization fusion protein, and / or an adapter fusion protein are expressed. The ENPs can comprise the one or more RNA cargo molecules. There are also provided populations of ENPs in some embodiments.