373 results about "Gene delivery" patented technology

The present disclosure provides systems and methods for processing cells. The systems of the present disclosure may include a compartment, a three-dimensional (3D) matrix, a fluid flow path, an analysis unit, a preservation unit, or any combination thereof. The methods of the present disclosure may process cells via, for example, expansion, culturing, gene delivery, activation, or any combination thereof. The systems and methods described herein may be useful for producing cell products including, for example, cell therapy products.

Disclosed herein are compositions of retroviruses and methods of using the same for gene delivery, wherein the retroviruses comprise a viral envelope protein comprising at least one mutation that diminishes its native function, a non-viral membrane-bound protein comprising a membrane-bound domain and an extracellular targeting domain.

The invention discloses a cationic super-deformation liposome capable of realizing gene transdermal transfection as well as preparation and application of the cationic super-deformation liposome, and belongs to the field of gene transdermal delivery. Materials such as low-molecular-weight polyethyleneimine, lipidosome and Tween 80 are adopted, and the components are safe and simple; polyethyleneimine is used as a conjugation carrier of the gene to improve the binding capacity of the gene, liposome is used as a delivery carrier to improve the skin delivery capacity of the gene, and Tween 80 is used for improving the stability and transdermal transfection capacity of the carrier again, so that non-invasive targeted transdermal delivery of the gene is realized; in vitro stability is high, gene degradation can be effectively inhibited, and meanwhile in vitro cell experiments, high transfection efficiency and low toxicity are achieved; the cationic super-deformed liposome can successfully realize high-efficiency transdermal penetration of the gene and effectively promote transfection expression of the gene in the skin at the same time, a new idea is provided for gene delivery, and the advantage of treating skin diseases through non-invasive delivery of the gene is expected to be fully exerted.

The present letter invention provides an engineered AAV capsid in which at least one protein on the capsid is modified to include an n-mer motif that promotes transduction of the capsid into the central nervous system (CNS) by interaction with a transferrin receptor. Further embodiments provide a carrier system comprising one or more carriers encoding an AAV capsid and a method of delivering a cargo to a CNS. The methods comprise administering an AAV capsid according to embodiments described herein in vivo or in vitro, and the AVV capsid comprises one or more carrier molecules.

The invention relates to the technical field of information, and provides a cross-platform global weed gene database unified building method which comprises the following steps: screening out a weed population having gene exchange characteristics with a target crop, identifying gene segments of gene exchange between the crop and weeds by adopting a gene comparison method, and determining a transmission path of resistance genes in interspecific hybridization; according to a gene comparison result, extracting transmission path data of the resistance gene, and analyzing the influence of resistance gene transmission on the genetic structure of the weed population in combination with the genetic structure characteristics of the weed population; calculating the frequency distribution of the resistance genes in different weed populations, judging the diffusion trend of the resistance genes in the weed populations according to the frequency distribution, generating a resistance gene diffusion map, and predicting the variation trend of the future weed population genetic structure based on a weed population genetic structure variation trend chart and the resistance gene diffusion map. And a global weed gene database is established, so that an effective weed management strategy can be formulated.

The present disclosure provides methods of gene transformation of sunflower based on Agrobacterium-mediated gene delivery to meristem cells of fresh imbibed / germinated sunflower seeds. One embodiment of the present disclosure is a method of directly transforming a sunflower from a mature seed with a heterologous polynucleotide, comprising: generating an explant from a germinated sunflower seed by removing cotyledons and primary leaves having intact meristem and tender shoot radicles; contacting the sunflower explant comprising the cotyledon with Agrobacterium comprising a heterologous polynucleotide in an infection medium supplemented with a plant hormone using vacuum and ultrasound treatment; co-culturing the explant from a germinating sunflower plant in a culture medium lacking the plant hormone in the presence of the Agrobacterium genus; culturing the mature seed explant in a regeneration medium comprising a selective agent; and culturing the seed with the regenerated tender shoots and with the secondary roots in a culture medium lacking the selective agent.

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.

Compositions of retroviruses and methods of using the same for gene delivery, wherein the retroviruses comprise a viral envelope protein comprising at least one mutation that diminishes its native function, a non-viral membrane-bound protein comprising a membrane-bound domain and an extracellular targeting domain.

The present invention relates to an exogenous target gene expression cassette for delivering an exogenous target gene to the retina, in particular AIPL1 to retinal pigment epithelial cells and photoreceptor cells, comprising an IRBP enhancer sequence, a rhodopsin kinase (RK) promoter sequence and a CAG intron sequence, which are operatively linked, and an exogenous target gene. The present invention also relates to a recombinant adeno-associated viral vector comprising a viral capsid comprising a capsid protein or a capsid protein variant and a viral vector genome comprising an expression cassette encoding for specifically expressing an exogenous target gene in retinal pigment epithelial cells and photoreceptor cells. The recombinant adeno-associated virus vector can be used for relieving or treating retinal degenerative eye diseases by intravitreal administration or subretinal administration.

A polyphenol modified vector, a gene delivery system, and the use thereof in preparing a gene drug. The polyphenol modified vector comprises a vector and a polyphenol modifying same. The gene delivery system comprises the polyphenol modified vector and a gene loaded on the polyphenol modified vector.

The invention belongs to the technical field of biological medicines, discloses a preparation method of a pcDNA3.1-GH-loaded chitosan nanoparticle gene delivery system and an application of the pcDNA3.1-GH-loaded chitosan nanoparticle gene delivery system in fishes, and aims to solve the problems that the existing gene delivery technology is complicated in operation, the public are not trusted to transgenic foods and the growth rate of the fishes is low. The invention provides an oral chitosan nano-gene delivery system, which is characterized in that pcDNA3.1-GH-loaded chitosan nanoparticles are constructed by compounding a lateolabrax japonicus growth key gene gh with chitosan. Results show that the gene-loaded chitosan nanoparticles can effectively enter cells and realize the expression of exogenous genes, almost have no toxic effect, can achieve an instantaneous transgenosis effect without modifying the genome of an organism, and can significantly improve the growth performance of cultured fishes at the same time. The method has high efficiency, safety and economical efficiency, and provides a reproducible solution for industrialization of an aquaculture sex control technology.

A system for delivering a payload nucleic acid into target cells of a subject and production of a payload (or payloads) encoded by the payload nucleic acid in the cells. The system includes a Bifidobacterium sp. bacterium comprising a plasmid and a transporter nucleic acid, the transporter nucleic acid configured for expression in the bacterium. The transporter nucleic acid encodes a transporter polypeptide comprising, in an amino-terminal to carboxy-terminal order, a bacterial secretion signal peptide, a DNA-binding domain to bind the plasmid, and a cell penetrating peptide. The transporter polypeptide complexes with the plasmid and transports the plasmid from the bacterium into the target cells. The plasmid encodes one or more payloads (protein and / or ribonucleic acid) for production in the target cells. The target cells may be colonic cells. When the payload(s) include an antigen, the system may be a DNA vaccine.

The invention relates to a biological medicine technology, and discloses chloroquine lipid, a preparation method and application thereof, and lipid nanoparticles containing the chloroquine lipid. The chloroquine lipid is synthesized from chloroquine substances and alkylene oxide through a ring-opening reaction, and the chloroquine substances are selected from at least one of chloroquine, hydroxychloroquine, chloroquine derivatives and hydroxychloroquine derivatives. The lipid nanoparticles contain the chloroquine lipid, cationic lipid, phospholipid, PEG (polyethylene glycol) lipid and cholesterol. The chloroquine lipid can be used as a lipidated autophagy inhibitor, can endow the LNPs carrier with an autophagy inhibition function, and realizes the autophagy inhibition effect of'time-space synchronization ', so that the obstacle of'autophagy lysosome degradation' is broken through, and the gene delivery efficiency is enhanced.

The invention belongs to the technical field of drug co-delivery, and particularly relates to a nano-platform based on attenuated bacterial outer membrane vesicles and capable of achieving co-delivery of siRNA and adriamycin and a preparation method of the nano-platform. The preparation method comprises the following steps: synthesizing an ROS response type cationic polymer PTP; the preparation method comprises the following steps: preparing aptamer-DOX; preparing an ROS (reactive oxygen species) response type positive electric nano core PTP / 47aD; extracting and purifying the [delta] msbB OMVs; synthesizing a target functional unit DSPE-PEG2k-Angiopep-2 (Distearoyl Phosphate Polyethylene Glycol 2k-Angiopep-2); finally, the ROS response type co-delivery nano platform AO (at) PTP / 47aD is prepared and obtained. The co-delivery nano-platform prepared by the invention is relatively small in particle size, uniform in morphology and relatively high in biological safety, and has no obvious damage to various tissues and visceral organs. The glioblastoma immunopotentiator can be used as a general platform for gene delivery, can also be used as an immune activator, is suitable for intravenous injection administration, and can comprehensively overcome immune resistance of glioblastoma.

Hydrodynamic injection of nucleic acid or protein for in vivo gene therapy to biliary duct, liver, pancreas, and kidney of a subject.

The present invention relates to a novel ionizable lipid and a lipid nanoparticle composition using same. Lipid nanoparticles formed using the novel ionizable lipid exhibit an excellent gene encapsulation rate and intracellular / in vivo gene delivery rate, and exhibit excellent muscle delivery of genes through local injection, and thus can be effectively used as a composition for drug delivery.

The invention discloses a method for preparing a heterozygous exosome through DNA zipper mediated membrane fusion. A DNA zipper structure (ZDC / cZDC) modified by cholesterol is designed and anchored to the surface of a BMSC source exosome and the surface of a lipidosome membrane loaded with siRNA, membrane fusion is achieved through DNA complementary pairing, and after DNase I enzymolysis, the heterozygous exosome carrying siRNA and over-expressed CD146 at the same time is obtained. The method has the advantages of high fusion efficiency and uniform particle size, solves the problems of low drug loading efficiency and poor targeting property of the traditional exosome, and is suitable for gene-drug collaborative delivery.

The invention discloses a nuclear targeting peptide modified DNA nano-particle based on a microfluidic technology and a preparation method and application thereof, and relates to the technical field of biological medicine, a poly (beta-amino ester) cationic polymer is used as a gene delivery carrier, the gene delivery carrier comprises a microtubule related sequence MTAS and a nuclear localization signal NLS oligopeptide, the gene delivery carrier and the plasmid DNA carrying the target gene are mixed to prepare nano-particles, and the plasmid DNA carrying the target gene is uniformly dispersed in the nano-particles by adopting a microfluidic mixing process; the nuclear targeting peptide modified DNA nano-particle is ingenious in structural design, the mixing uniformity of a nano-carrier and plasmid DNA is improved by adopting a micro-fluidic mixing process, the performance of the nano-particle is further improved by optimizing dialysis conditions, potential cytotoxicity and adverse effects are reduced, and the nuclear targeting peptide modified DNA nano-particle is suitable for large-scale production. And after transduction of non-activated T cells, strong tumor killing ability and cytokine secretion can be generated.

The present invention relates to a novel ionizable lipid and a lipid nanoparticle composition comprising same. Lipid nanoparticles formed from a novel ionizable lipid compound, according to the present invention, exhibit an excellent gene encapsulation rate and in vivo gene delivery rate, and moreover, exhibit an excellent gene delivery function even in a liver damage model, and thus may be usefully employed as a composition for drug delivery.

The invention discloses a chimeric antigen receptor modified cell drug as well as a preparation method and application thereof, and belongs to the technical field of cell drugs. A cell drug is obtained by introducing a chimeric antigen receptor targeting B cells and / or plasma cells into in-vitro or in-vivo immune cells through a gene delivery system, and target spots of the targeted B cells and / or plasma cells comprise CD19, BCMA, CD20, CD22, CD38, CD138, GPRC5D and SLAMF7. The chimeric antigen receptor modified cell drug can realize specific recognition of B cells and / or plasma cells and activate immune cells through a specific single-chain antibody fragment (scFv), and can specifically remove the B cells in vitro and in vivo, thereby preventing the generation of autoimmune antibodies and the formation of immune complexes, achieving the purpose of thoroughly treating diseases, and having good application prospects. The life quality of a patient is improved, the disease is finally cured, and the application potential and the commercial value are huge.

The invention discloses a preparation method and application of a response type cationized two-dimensional nano catalytic transfection agent, and belongs to the field of biology. According to the transfection agent disclosed by the invention, two-dimensional MXene (such as niobium carbide) is taken as a matrix, and the surface of the matrix is sequentially modified with a multi-amino cationic polymer (such as dendritic polyethyleneimine) and aldehyde group polyethylene glycol (CHO-PEG-CHO), so that PNb2C (at) PEG with pH responsiveness is formed. The preparation method comprises the steps of Nb2C nanosheet stripping, PEI cationization, PEG shielding modification and the like. Material characterization shows that the potential of the transfection agent is-12.5 mV (shielding positive charges) when the pH value is 7.4, the potential of the transfection agent is converted into + 14.0 mV (responding to a tumor acidic microenvironment) when the pH value is 6.5, and the transfection agent has the capability of catalyzing decomposition of active oxygen and can protect cells from oxidative damage. Compared with the traditional cationic liposome, the transfection efficiency is equivalent, but the toxicity is obviously reduced, the raw material cost is low, the gene load is high, and the cationic liposome is suitable for the field of gene delivery.

The present invention pertains to the technical field of biomedicine, and specifically relates to a gene delivery system and use thereof in the preparation of a tumor therapeutic drug. The present invention relates to a technical means for inducing differentiation of tumor cells into mature cells, which utilizes messenger ribonucleic acid to regulate the expression of HNF4α in tumor cells, inhibits the malignant phenotype of malignant solid tumor cells, and achieves the effect of treating malignant solid tumors, thereby being applied to a preparation method and use of a solid tumor drug.

The present invention discloses a mitochondrially targeted fluorinated ionizable lipid and its use as a mitochondrial gene delivery vector. A mitochondrially targeted fluorinated ionizable lipid is a compound of formula (I), or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein: a = an integer from 2 to 8, b = an integer from 4 to 8; and R1 is an ionizable lipid head group, comprising a mono- or polyamine containing a primary or tertiary amine structure. A mitochondrially targeted lipid carrier comprises the fluorinated ionizable lipid described herein, a cationic lipid, an auxiliary lipid, a structural lipid, and a functional polymer conjugated lipid modified with a mitochondrial targeting group. The fluorinated ionizable lipid gene delivery vector with mitochondrial targeting capability provided by the present invention has excellent biocompatibility, can simultaneously increase the cellular uptake and mitochondrial accumulation of gene drugs, improve the efficiency of mitochondrial gene transfection, and achieve efficient delivery of gene drugs to the mitochondrial matrix. #imgabs0#

The present disclosure relates to an approach, referred to as Regionally Activated Interstitial Drugs (RAID), that does not require viral vectors, but allows for tunable, noninvasive, long-term neuromodulation with small molecules. RAID utilizes noninvasive delivery of an engineered protein enzyme into the brain, which then binds to the brain parenchyma and can locally convert a blood-brain-barrier (BBB)-permeable inert prodrug into an active neuromodulatory drug. As long as the RAID enzyme is present in the parenchyma, localized neuromodulation can be achieved with systemic administration of the BBB-permeable prodrug even in the absence of the opened BBB. Alternatively, gene delivery encoding the RAID enzyme offers prolonged expression and precise spatial control, enabling long-term and adaptable neuromodulation.

The application discloses application of a reagent for detecting LRRN3 expression level in preparation of a benign prostatic hyperplasia diagnosis product. It is proved through cell function experiments and animal experiments that overexpression of the LRRN3 gene can inhibit the proliferation of prostate cells, block the cell cycle and promote cell apoptosis, thereby effectively inhibiting the prostatic hyperplasia. The discovery provides a new target and treatment strategy for the treatment of the prostatic hyperplasia, and provides a brand-new thought and method for the treatment of the prostatic hyperplasia. Based on the research results, a gene therapy drug taking the LRRN3 gene as a target can be further developed, for example, a lentivirus vector carrying the LRRN3 gene or other gene delivery systems are constructed and used for the treatment of the prostatic hyperplasia. In addition, the LRRN3 gene can be combined with other treatment methods to improve the treatment effect.

The present disclosure provides compositions and methods for delivering a gene of interest to a subject. Aspects of the application relate to nucleic acids encoding modified retroelement-derived polypeptides and gene delivery constructs that can direct integration of a nucleic acid sequence into a target nucleic acid (e.g., a genome of a subject).

Developing vehicles that efficiently deliver genes throughout the human central nervous system (CNS) will broaden the range of treatable genetic diseases. Applicants engineered an AAV capsid, BI-hTFRl, that binds human Transferrin Receptor (TfRl), a protein expressed on the blood-brain barrier (BBB). BI-hTFRl was actively transported across a human brain endothelial cell layer and, relative to AAV9, provided 40-50 times greater reporter expression in the CNS of human TFRC knock-in mice. The enhanced tropism was CNS-specific and absent in wild type mice. When used to deliver GBA1, mutations of which cause Gaucher disease and are linked to Parkinson's disease, BI-hTFRl substantially increased brain and cerebrospinal fluid glucocerebrosidase activity compared to AAV9.

A portable in vitro blood cell gene editing or modification system comprises: a fluid inlet (111) and a fluid outlet (112); processing units (1200, 1201, 1202, 1203), wherein the processing units (1200, 1201, 1202, 1203) are configured to perform gene editing or gene modification on target cells in the blood input through the fluid inlet (111) by gene delivery and are also configured to remove non-treatment-requiring substances in the treated blood, and the processing units (1200, 1201, 1202, 1203) are fluidically connected between the fluid inlet (111) and the fluid outlet (112).

This invention provides a multifunctional nanodelivery system integrating gene delivery and CT tracking. The multifunctional nanodelivery system includes a gene delivery vector and an HGF plasmid gene loaded on the gene delivery vector; the gene delivery vector comprises gold nanoparticles coated with protamine sulfate. The gene delivery vector AuPS provided by this invention has excellent cell membrane transport and nuclear localization capabilities, enabling the HGF plasmid gene to efficiently enter cells and be expressed in the nucleus. The multifunctional nanodelivery system provided by this invention can be used for cell function regulation and tracking of therapeutic cells such as stem cells.