304 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.

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 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 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 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 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.

The present invention relates to the field of gene therapy in the medical field, and in particular to the use of overexpressing normal genes to restore hearing in patients with hereditary hearing loss caused by gene mutations or deletions. The present invention relates to a dual vector system expressing an OTOF protein. The dual vector system comprises two segments of nucleotide sequence, the first segment comprising two ITR sequences and a gene expression cassette inserted between the ITR sequences, and the second segment comprising two ITR sequences and a gene expression cassette inserted between the ITR sequences. An adeno-associated virus packaged with the vector is also provided. The vector and virus can restore hearing in both ears by administering them to one ear, in the field of large-scale dual vector gene delivery for hearing loss gene therapy.

The invention relates to the field of biotechnology and targeted therapy, in particular to a recombinant construct, a recombinant oncolytic virus and construction and application of the recombinant oncolytic virus. The virus takes a wild poxvirus genome as a skeleton, thymokinase TK genes are deleted through homologous recombination, and a poxvirus P-se / l promoter is used for promoting expression of a CD19 membrane localization antibody. The constructed recombinant oncopoxvirus aCD19-TM-OVV can improve the infection efficiency and gene delivery efficiency on B lymphoma in a CD19 antigen target-dependent manner, promote virus replication of the oncopoxvirus in CD19 positive B lymphoma cells, and significantly enhance the tumor growth inhibition effect on the CD19 positive B lymphoma cells in vitro and in mouse B lymphoma models.

The present invention relates to a gene carrier including a nucleic acid molecule containing a gene of interest conjugated to the surface of a metal nanoparticle, which is delivered into cells and expressed, a use thereof, a gene expression method using the same, and a method of preparing the same.

The invention relates to a Sebastes schlegeli endogenous retrovirus envelope protein Penv, a lentiviral vector and application thereof, and belongs to the field of genetic breeding of molecular biology, and the amino acid sequence of the envelope protein Penv is as shown in SEQ ID NO.1. The invention further provides an in-vitro assembly system, a transformant and a kit containing membrane fusion protein particles and lentiviral particles of the envelope protein Penv and application of the envelope protein Penv. VSVG protein is replaced with Penv protein from sclerobone fish, so that the transduction efficiency of the lentiviral particles to sclerobone fish cells is effectively improved, and the transduction efficiency of the lentiviral particles to the sclerobone fish cells is improved. And efficient gene delivery is realized. Meanwhile, as the endogenous Env protein, the Env protein overcomes the immunological rejection of a host to the exogenous Env protein, and also has the potential of in-vivo application.

The invention relates to the field of biological medicines, in particular to a self-replicating RNA (Ribonucleic Acid) vector, a gene delivery system and application of the gene delivery system. By systematically optimizing the 5 'UTR end structure of the self-replicating RNA, the innate immune response of the self-replicating RNA can be regulated and controlled, the replication characteristic of the self-replicating RNA is maintained, the cytotoxicity is reduced, the efficient expression characteristic is maintained, and a new strategy is provided for developing a low-toxicity and efficient gene therapy vector.

The disclosure provides for recombinantly modified Zika-based vectors that can be used in gene therapy applications.

The invention relates to a gene delivery system for cytoplasm specific expression of PPM1K as well as a preparation method and application of the gene delivery system, and belongs to the technical field of preparation of gene delivery systems. The gene delivery system is preferably an adeno-associated virus (AAV), and the preparation method of the gene delivery system specifically comprises the following steps: inserting a PPM1K gene or a functional variant thereof into a vector, and adding a detectable label at a C terminal to form a recombinant plasmid; transforming the recombinant plasmids into competent escherichia coli, amplifying, and screening and extracting plasmids to obtain recombinant AAV plasmids; co-transfecting the recombinant AAV plasmid, the helper plasmid and the capsid plasmid into packaging cells by using a transfection reagent, collecting the cells and culturing supernate after transfection, and adding a freeze thawing buffer solution for repeated freeze thawing to obtain a cell lysis solution; centrifuging the cell lysis solution, taking supernate, purifying and filtering. According to the invention, the specific expression of the cell compartment of the therapeutic gene is realized through the vector design, and the obvious therapeutic effect and the safety advantage are shown.

This invention relates to a polypeptide for gene delivery, a polypeptide / nucleic acid molecular complex prepared therefrom, and its applications. The polypeptide of this application has the structure shown in Formula I, wherein Formula I contains an immune cell targeting group represented by Y. The polypeptide developed in this application, as a gene delivery carrier, has a highly efficient nucleic acid loading capacity. Furthermore, it exhibits high delivery efficiency to immune cells both in vitro and in vivo, thus showing broad application prospects in the immune cell-targeted delivery of genes.

The present invention relates to a pH-sensitive cationic lipid, a lipid nanoparticle, a pharmaceutical composition containing the lipid nanoparticle, and a use of the lipid nanoparticle. A lipid nanoparticle according to the present invention is useful as a gene delivery carrier that can be selectively delivered to the liver or spleen, the lipid nanoparticle containing a pH-sensitive cationic lipid represented by the following formula (I): (In formula (I), a represents an integer of 3-5; b represents 0 or 1; r1 and R2 each independently represent a group represented by general formula (A); in formula (A), R11 and R12 each independently represent a linear or branched C2-15 alkyl group; c represents 0 or 1: v represents an integer from 4 to 12; x represents a group represented by general formula (B) or a 5-to 7-membered non-aromatic heterocyclic group; in formula (B), d represents an integer of 0-3; r3 and R4 each independently represent a C1-4 alkyl group or a C2-4 alkenyl group, and R3 and R4 may be bonded to each other to form a 5-to 7-membered non-aromatic heterocyclic ring.