183 results about "Gene delivery" patented technology

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.

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).

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

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.

The present invention provides a multiomics approach, which integrate single-cell RNA-sequencing (scRNA-seq) and spatiotemporal transcriptomics (ST) offering potential for dissecting transcriptional networks and revealing cell-cell interactions involved in biomolecular pathomechanisms. The present invention also provides a multimodal approach combining high-throughput scRNA-seq and ST to elucidate XLRS-specific transcriptomic signatures in two XLRS-like models with retinal splitting phenotypes, including genetically engineered (Rs1emR209C) mice and patient-derived retinal organoids harboring the same patient-specific p.R209C mutation. Through multiomics transcriptomic analysis, the endoplasmic reticulum (ER) stress / eIF2 signaling, mTOR pathway, and the regulation of eIF4 and p70S6K pathways as chronically enriched and highly conserved disease pathways between two XLRS-like models are identified. Western blots and proteomics analysis validated the occurrence of unfolded protein responses, chronic eIF2α signaling activation, and chronic ER stress-induced apoptosis. Furthermore, therapeutic targeting of the chronic ER stress / eIF2α pathway activation synergistically enhanced the efficacy of AAV mediated RS1 gene delivery, ultimately improving bipolar cell integrity, postsynaptic transmission, disorganized retinal architecture and electrophysiological responses. Collectively, the complex transcriptomic signatures obtained from Rs1emR209C mice and patient-derived retinal organoids using the multiomics approach provide opportunities to unravel potential therapeutic targets for incurable retinal diseases, such as XLRS.

The invention belongs to the technical field of biological medicine, and discloses a medicine for in-vivo engineering CAR-T and a preparation method thereof. The drug provided by the invention comprises a first RNA and a second RNA which are used for coding a chimeric antigen receptor in a specific molar ratio, the second RNA is used for coding at least two cytokines of CCL19, IL-17, IL-15, IL-2 or IL-24, by adopting the drug, the gene delivery efficiency and targeting of in-vivo engineered CAR-T can be improved, better T cell transformation and CAR + T cell generation effects are realized, the CAR-T cell depletion is reduced, and the drug has a good application prospect. According to the present invention, the CAR-T gene is constructed, such that the CAR-T gene can survive for a long time in the tumor microenvironment and continuously provide the treatment effect, has the excellent anti-tumor treatment effect, has the excellent application prospect in the in-vivo engineering CAR-T treatment, and has the important significance on the promotion of the efficient, safe and economical development of the CAR-T treatment.

The present document describes a pharmaceutical composition comprising a) a lipid nanoparticle operable to encapsulate a therapeutic agent, comprising a core and an external surface, said therapeutic agent being encapsulated within said core; said lipid nanoparticle having a size of said lipid nanoparticle of from about 30 to about 80 nm, or a pegylated lipid comprising a distearoyl-rac-glycerol (DSG) – PEG and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- (DSPE) – PEG - DBCO; or a combination of: a size of from about 30 to about 80 nm and a pegylated lipid comprising a DSG-PEG and DSPE-PEG-DBCO; and b) an antibody or antigen-binding fragment thereof operable to transmigrate the blood-brain barrier (BBB), wherein the antibody or antigen-binding fragment thereof comprises complementarity determining regions (CDR1, CDR2 and CDR3), operably linked to said external surface of said lipid nanoparticle.

The invention discloses a redox sensitive cationic polymer gene vector as well as preparation and application thereof. According to the invention, hydrophobic small molecules with oxidation / reduction responsive S-S bonds are adopted to carry out side chain modification on polyglycidyl amine, and the cationic polymer gene delivery carrier material with specific tumor microenvironment response capability is prepared. The material has good biocompatibility, and can effectively load siRNA molecules and form siRNA compound nanoparticles with good stability and excellent gene transfection capacity. The compound nanoparticles can be effectively absorbed by cells, and can effectively respond to an oxidation / reduction tumor microenvironment to realize targeted release of siRNA. The oxidation / reduction response cationic polymer gene vector provided by the invention has a relatively great clinical application prospect.

The invention relates to the combination of a cell-selective promoter to drive the N-terminal part of the transgene and a compact ubiquitous promoter with similar expression levels to drive the C-terminal part of the transgene (or vice versa) for dual AAV intein-mediated delivery to obtain cell-selective, efficient transgene expression.

To provide a CRISPR gene delivery system that ensures robust expression of CRISPR proteins and avoids the risk of genomic integration. [Solution] A synthetic, non-infectious, self-replicating RNA vector encoding a CRISPR protein is provided. Each self-replicating RNA vector contains sequences encoding multiple non-structural replication complex proteins derived from alphaviruses, and sequences encoding a CRISPR protein. A method for genome editing is also provided, which involves introducing a synthetic self-replicating RNA vector into a cell along with at least one corresponding guide RNA.

Compositions comprising lipidoid compounds, methods of preparing such compositions, and the use of these compositions in gene delivery applications are disclosed.

The present invention relates to a phage-based gene delivery system targeting human cells or animal cells, including immune cells, other human cells and cancer cells. In particular, the present invention relates to novel phage particles and associated phagemid expression systems and their production for the delivery of transgenes, comprising DNA encoding pathogen antigens, to human immune cells, suitable for use in vaccines and vaccine development against infectious diseases and cancers.

The invention relates to a gene delivery vector, a gene delivery system and a preparation method and application thereof. The gene delivery system provided by the invention comprises the gene delivery carrier provided by the invention and lipid nanoparticles; the lipid nanoparticles encapsulate the gene delivery vector. In the prior art, related researches on treatment of metabolic disorder diseases or diseases (such as OTCD) based on lipid nanoparticle LNP delivery are not found temporarily, so that the carrier containing the OTC-circRNA drug gene based on LNP delivery is constructed for the first time, and the carrier can be used for treating the metabolic disorder diseases or diseases. The effectiveness and safety of treatment are researched in vivo and in vitro, a new scheme is provided for clinical treatment of patients with gene defects, and the application value is important. The OTC-circRNA-encapsulated lipid nanoparticles disclosed by the invention are good in stability in vivo, good in safety and long in curative effect lasting time.

Provided are therapies comprising immune effector cells, such as T cells, engineered to express an antigen receptor, such as a T cell receptor or a chimeric antigen receptor.SOLUTION: It is demonstrated that antigen receptor-engineered immune effector cells can be generated in vitro / ex vivo as well as in vitro by delivering a nucleic acid encoding an antigen receptor for genetic modification to a cell using a particle comprising the nucleic acid and a targeting molecule for targeting the immune effector cell, wherein the targeting molecule is a designed ankyrin repeat protein (DARPin). In particular, DARPins are provided that are high affinity binders for CD8 binding to CD8 receptors on human and non-human primate (NHP) cells. Nanoparticles functionalized with CD8 targeting DARPins (CD8 - DARPins) can deliver genes exclusively and specifically to human CD8 + T cells in vitro and in vivo.SELECTED DRAWING: None

The invention provides a gH625-H2A histone as well as chromatin and application thereof. The histone is prepared by adding peptide gH625 into histone H2A; the application comprises the application of the gH625-H2A histone and the chromatin thereof in preparation of drugs or drug delivery systems and the application of the gH625-H2A histone and the chromatin thereof in preparation of skin care products and cosmetics. The invention provides the gH625-H2A histone and the chromatin thereof, the histone and the chromatin have strong cell penetration and skin permeation effects, the histone and the chromatin are expected to promote the development of a transdermal gene delivery system and biological medicines and skin care products, and the prepared biological medicines and the skin care products have the advantages that the development of the transdermal gene delivery system and the biological medicines and the skin care products is facilitated; passive skin delivery of nucleic acids, small peptides, growth factors and enzymes is achieved without physical or chemical intervention.

Nanoparticle compositions for delivery of nucleic acids to subjects including aminoalkyl branched lipid-like molecules as carriers, and therapeutic or immunogenic nucleic acid agents enclosed within the nanoparticle containing are described. Also provided are methods for treating or preventing diseases or conditions in a subject by administering the nanoparticle compositions that provide immune responses and synergistic therapeutic or preventive effects.

Provided are methods for inserting a large gene / polynucleotide between about 4.5Kb and about 8Kb and lacking a selection marker into a target genomic position in a cell by delivering the gene / polynucleotide by two AAV vectors in the presence of a p53-binding protein 1 (53BP1) inhibitor and a DNA-dependent protein kinase catalytic subunit (DNA- PKcs) inhibitor. The disclosed methods improve large gene insertion by at least 10-fold and obviate the need for a selection marker in the vector design, thereby providing more room in the AAV vector for gene delivery.

The invention particularly relates to a sebastes schlegeli endogenous retrovirus envelope protein percomORF, a lentiviral vector and application of the sebastes schlegeli endogenous retrovirus envelope protein percomORF and the lentiviral vector, and belongs to the field of genetic breeding of molecular biology, and the envelope protein percomORF has an amino acid sequence as shown in SEQ ID NO.1. The invention also covers a membrane fusion protein particle constructed based on the protein, a system for in-vitro assembly of lentivirus particles, a corresponding transformant and a matched kit. By replacing conventional VSVG protein with percomORF protein from sclerobone fish, the infection and transduction efficiency of lentivirus on sclerobone fish cells can be effectively enhanced, and more efficient gene delivery is realized. Besides, the protein belongs to host endogenous Env protein and is beneficial to avoiding immunological rejection caused by introduction of foreign protein, so that the protein has good potential in in-vivo gene delivery application.

The present invention relates to a novel ionized lipid and a lipid nanoparticle composition containing the same. The lipid nanoparticles formed by the novel ionized lipid compound according to the present invention are characterized by exhibiting excellent gene encapsulation rate and in vivo gene delivery rate, while also demonstrating excellent gene delivery function in a liver injury model, and thus can be usefully utilized as a drug delivery composition.

The invention discloses a kelp gametophyte gene editing method and application, and belongs to the technical field of gene editing, the kelp gametophyte gene editing method comprises the following steps: preparing a kelp gametophyte receptor; assembling an RNP complex and preparing a microcarrier; introducing the RNP compound into a kelp gametophyte by using a gene gun; and recovering culture and screening. According to the technical scheme, the dependency of a microinjection technology on precise instruments and professional operation skills is eliminated, efficient gene delivery can be achieved through a standardized gene gun operation process, the technical threshold is greatly reduced, and the kelp gametophyte gene editing method has remarkable technical advantages. According to the method, the high-throughput characteristic of a gene gun technology is fully exerted, multiple mutants can be obtained through one-time bombardment, the experiment efficiency is greatly improved, and powerful support is provided for kelp large-scale gene function research and molecular breeding.

The invention belongs to the technical field of plant gene expression and editing, and discloses composite lipid nanoparticles for plant cell gene delivery as well as a preparation method and application of the composite lipid nanoparticles. According to the composite lipid nanoparticle provided by the invention, the lipid nanoparticle is used as a carrier for loading an active substance, meanwhile, a hydrolase composition is introduced to the surface of the lipid nanoparticle through the strong non-covalent acting force between the streptavidin and the biotin, and the hydrolase composition is introduced to the surface of the lipid nanoparticle through the strong non-covalent acting force between the streptavidin and the biotin; the composite lipid nanoparticles have excellent delivery efficiency on plant cells under the conditions that the plant cell structure is not damaged and the metabolic state of the plant cells and the physiological state of the plant are not influenced, and have very excellent application prospects in the plant breeding technology.

The invention relates to the field of gene therapy. In addition the invention relates to the field of interfering RNA and / or microRNA (miRNA). In particular the invention relates to gene therapy involving such miRNA's and more in particular to methods and means to improve delivery of said miRNAs to target cells of a patient. The invention provides for a gene delivery vehicle for use in delivery of a miRNA to a cell resulting in silencing of a desired gene and whereby spread of said miRNA to other non-transduced cells results in silencing of said desired gene in said non-transduced cells.

The present application relates to the technical field of bioengineering, and particularly relates to a pIX region antigen-carrying capsid armed adenovirus, a construction method and application. An exogenous antigen gene is introduced into a pIX region of a minor capsid protein of a type 5 adenovirus to form a capsid armed adenovirus; the type 5 adenovirus specifically has an E1 region and an E3 region deletion. The construction method uses pIX as a display platform, can present an exogenous antigen on the virus surface with high density and high repeatability, greatly improves the effective concentration of the antigen, and is expected to induce stronger and more persistent specific immune responses; the modified pIX protein has less influence on the packaging, assembly, structural stability of the virus and the infection ability on target cells; the adenovirus can realize the dual functions of "gene delivery" and "surface antigen presentation", and provides an innovative technical platform for developing multifunctional and high-titer vaccines or gene therapy drugs.

Nanoparticle compositions for delivery of nucleic acids to subjects including aminoalkyl branched lipid-like molecules as carriers, and therapeutic or immunogenic nucleic acid agents enclosed within the nanoparticle containing are described. Also provided are methods for treating or preventing diseases or conditions in a subject by administering the nanoparticle compositions that provide immune responses and synergistic therapeutic or preventive effects.