13 results about "Mrna transfection" patented technology

The invention provides a targeted mRNA delivery system of muscle tissues and / or muscle cells based on aptamer functionalized LNP (Apt-LNP), the delivery system can significantly improve mRNA transfection of the muscle tissues, and meanwhile, mRNA expression in main organs such as liver and spleen is greatly reduced. The expression intensity of muscle tissue in-situ mRNA is improved through modification of the aptamer, meanwhile, mRNA expression in main organs such as the liver and the spleen is greatly reduced, and side effects caused by off-target of mRNA infectious disease vaccines are expected to be avoided. The method is expected to be applied to the field of infectious disease mRNA vaccines The invention also provides a targeting mRNA delivery system of lymph node tissues and / or immune cells based on the aptamer functionalized LNP (Apt-LNP). Compared with an existing lymph node targeting system, the Apt-LNP modified by the aptamer not only can realize lymph node mRNA targeting, but also can further target immune cells, and is expected to be applied to the field of tumor mRNA vaccines to enhance the curative effect of tumor vaccines.

A cationic lipid compound, and a preparation method therefor and use thereof are provided. The cationic lipid compound features a hydroxyl group at the head part, and its overall structure resembles a cone with a small head and a large tail. The LNPs prepared using the cationic lipid compounds with the aforementioned optimal structure usually exhibit enhanced biocompatibility and higher in vivo mRNA transfection efficiency, achieving unexpected technical effects. The synthesis route of the cationic lipid compounds is straightforward and practicable, with inexpensive and readily available raw materials, facilitating industrial production. Furthermore, the LNPs produced from the cationic lipid compounds possess a stable nanostructure that can be stored at low temperatures for a long time, thereby prolonging the shelf life of the pharmaceutical products while reducing the transportation requirements.

This invention belongs to the field of biomedical technology, specifically relating to a delivery system for type III collagen mRNA and its applications. The nucleic acid delivery system of this invention includes a delivery carrier and a delivered nucleic acid, wherein the nucleic acid is collagen mRNA, and the delivery carrier includes one or more of modified amino acids, growth factors, and polymeric materials. Through intradermal injection, the delivery system of this invention can be administered to the dermal layer of the skin and enter relevant cells, utilizing endogenous cellular proteins to achieve mRNA transfection, forming natural human type III collagen. This invention avoids the immunogenicity risks and structural inactivation problems associated with exogenous collagen injections, and can efficiently and safely replenish non-regenerative type III collagen in tissues. It can be used for various indications such as treating skin aging, promoting wound healing, reducing scar formation, and improving vascular elasticity.

The invention discloses a linear poly (beta-amino ester) compound loaded with hepatocyte growth factors as well as a preparation method and application of the linear poly (beta-amino ester) compound, and belongs to the technical field of biological medicines. The compound is obtained by self-assembly of linear poly beta-amino ester DD90-C12-DMEN and HGF mRNA in a buffer solution, the compound is suitable for aerosol inhalation delivery, higher mRNA transfection efficiency is obtained in lung-related epithelial / stromal cells, macrophages and other cells difficult to transfect, and particularly, the compound shows remarkable transfection advantages on the macrophages.

Leveraging the extensive surface area of the lungs for gene therapy, inhalation route offers distinct advantages for delivery. Clinical nebulizers that employ vibrating mesh technology are the standard choice for converting liquid medicines into aerosols. However, they have limitations when it comes to delivering mRNA through inhalation, including severe damage to nanoparticles due to shearing forces. A microfluidic aerosolization platform (MAP) can preserves the structural and physicochemical integrity of lipid nanoparticles, enabling safe and efficient mRNA delivery to the respiratory system. Results demonstrated the superiority of the novel microfluidic aerosolizer over the conventional vibrating mesh nebulizer, as it avoided problems such as particle aggregation, loss of mRNA encapsulation, and deformation of nanoparticle morphology. Notably, aerosolized nanoparticles generated by the microfluidic aerosolization platform led to enhanced transfection efficiency across various cell lines. In vivo experiments with mice that inhaled these aerosolized nanoparticles revealed successful, lung-specific mRNA transfection without observable signs of toxicity. This pioneering MAP represents a significant advancement for the pulmonary gene therapy, enabling precise and effective delivery of aerosolized nanoparticles.

The invention discloses a guanidyl lipid compound and application thereof, and belongs to the technical field of medicines. The structural general formula of the compound is as shown in any one of formula (I) to formula (IV), and guanidyl of the molecule is helpful to be combined with mRNA and other nucleic acid drugs and assists nucleic acid molecules in entering cells to play a role. The invention discloses various applications of the guanidyl lipid molecule. On one hand, the molecules can be used as a transfection enhancer to be added into four-component lipid nanoparticles in a small amount, so that the in-vivo and in-vitro mRNA transfection effects of the original lipid nanoparticles are enhanced; on the other hand, the reagent can be used as a single-component transfection reagent to directly deliver mRNA into cells to realize mRNA transfection. Under the applications, the guanidyl lipid molecules show relatively good nucleic acid delivery and transfection capacities, and have important significance in promoting the development of nucleic acid delivery.

To provide mRNA transfection of immune cells.SOLUTION: The present disclosure relates to methods of modifying immune cells by delivering a modified messenger RNA (mRNA) encoding a chimeric antigen receptor (CAR) and modified immune cells comprising the CAR. The present disclosure encompasses, inter alia, methods, systems, and compositions for modifying immune cells, including monocytes, macrophages, and / or dendritic cells. In some embodiments, the provided methods, systems, and / or compositions provide for enhanced production and / or enhanced properties of modified immune cells.SELECTED DRAWING: Figure 1A

Lipid nanoparticles (LNPs) are widely used for RNA delivery but are limited by inefficient RNA release following endosomal escape. Disclosed herein are hybrid polymer-lipid nanoparticles (PLNPs) incorporating acid-responsive poly(lactic acid)-block-poly(carboxybetaine) zwitterionic polymers to enhance RNA delivery efficiency. The polymers are cationic at physiological pH to enable RNA complexation but become neutral at endosomal pH, reducing RNA binding affinity and promoting release. These polymers were integrated into clinically approved LNP formulations to form PLNPs. The resulting PLNPs showed up to a 5.4-fold decrease in siRNA IC50 values and a 4-fold increase in mRNA transfection across multiple cell lines. Enhanced cytosolic RNA levels were confirmed via confocal microscopy, with uptake and endosomal escape comparable to standard LNPs. The improvement in transfection efficiency was lost when acid-inert polymers were used, confirming the role of the acid-responsive polymers. This approach provides a versatile platform to improve RNA delivery from existing LNP systems.

The invention discloses a glycoside sterol component lipid nanoparticle for regulating and controlling mRNA transfection as well as a preparation method and application of the glycoside sterol component lipid nanoparticle, and belongs to the technical field of pharmaceutical preparation preparation. The nanoparticle is prepared from DLin-MC3-DMA, DOPE, different glycosides or sterols and DSPE-PEG-GSH. The different glycosides or sterols comprise amygdalin Amy, beta-sitosterol, stigmasterol Sti, ginsenoside Rg1 and salidroside Sal. Stigmasterol can improve enrichment of LNP in the spleen, ginsenoside can adjust immunity and enhance the anti-tumor immune effect, the preparation method is simple, needed equipment is conventional equipment, large-scale production can be achieved, and therefore the stigmasterol and ginsenoside compound has good industrial application value and market prospects.

The invention discloses an imidazole ionizable lipid and a preparation method and application of metal coordination lipid nanoparticles of the imidazole ionizable lipid. Specifically, 32 kinds of imidazole ionizable lipids are designed and synthesized, and BR5-2 LNPs with the optimal mRNA delivery performance is obtained through screening. On the basis of the coordination effect of imidazole and Zn, the metal coordination lipid nanoparticles Zn-BR5-2 NAs are constructed. An XPS result proves that Zn and imidazole nitrogen are coordinated. The nanoparticles have excellent performance in the aspects of mRNA transfection efficiency, cellular uptake and lysosome escape, and can significantly promote the dendritic cell maturation and antigen presentation capability. In-vivo experiments show that the Zn-BR5-2 NAs has a good spleen targeting property. In a B16F10-OVA melanoma model, the Zn-BR5-2 NAs loaded with OVA mRNA (messenger Ribonucleic Acid) realizes a remarkable tumor prevention and treatment effect. According to the mRNA vaccine based on Zn-BR5-2 NAs, the anti-tumor effect is remarkably improved by enhancing immune response, an effective strategy is provided for tumor immunotherapy, and the mRNA vaccine based on Zn-BR5-2 NAs has wide application prospects.

The invention relates to the technical field of gene engineering, in particular to coding nucleic acid of Cre recombinase and application of the coding nucleic acid. The Cre recombinase is subjected to codon optimization of four versions, the protein expression quantity of the obtained Cre recombinase is remarkably improved compared with that of a wild type and other contrasts, the mRNA transfection reagent prepared from the nucleic acids can have good transfection efficiency, and the effect of a Cre recombinase system can be more effectively played when the mRNA transfection reagent is transferred into cells, particularly 293T cells.

The invention provides a preparation method and application of an in-vivo CAR-T cell for treating interstitial lung disease, and provides a T cell of a chimeric antigen receptor which is modified by genetic engineering and is used for expressing targeted fibroblast activating protein. A targeted fibroblast activation protein (FAP) CAR-T cell therapy model is constructed by targeting CD5 entrapped mRNA nano-liposome (LNP) transfection and lentiviral vector, and the method comprises the following steps: firstly, verifying the difference of the killing ability of FAP CAR-T constructed by CD5 LNP-mRNA and lentivirus in a 293T cell which stably co-expresses FAP, Luciferase and mCherry, and then verifying the difference of the killing ability of FAP CAR-T constructed by LNP-mRNA and lentivirus in the 293T cell which stably co-expresses FAP, Luciferase and mCherry; further verifying the effectiveness of the CAR-T cells constructed by transfecting the CD5 LNP-mRNA on cell lines of human fibroblasts (CDD19Lu, LL29 and LL97A) and primary fibroblasts of human and mice in vitro, and further verifying the effectiveness and safety of the CD5 LNP-FAP CAR-T in treatment of pulmonary fibrosis through in-vivo experiments in animals. A novel and effective anti-fibrosis treatment thought is provided for patients with fibrosis interstitial lung diseases.

Leveraging the extensive surface area of the lungs for gene therapy, inhalation route offers distinct advantages for delivery. Clinical nebulizers that employ vibrating mesh technology are the standard choice for converting liquid medicines into aerosols. However, they have limitations when it comes to delivering mRNA through inhalation, including severe damage to nanoparticles due to shearing forces. A microfluidic aerosolization platform (MAP) can preserves the structural and physicochemical integrity of lipid nanoparticles, enabling safe and efficient mRNA delivery to the respiratory system. Results demonstrated the superiority of the novel microfluidic aerosolizer over the conventional vibrating mesh nebulizer, as it avoided problems such as particle aggregation, loss of mRNA encapsulation, and deformation of nanoparticle morphology. Notably, aerosolized nanoparticles generated by the microfluidic aerosolization platform led to enhanced transfection efficiency across various cell lines. In vivo experiments with mice that inhaled these aerosolized nanoparticles revealed successful, lung-specific mRNA transfection without observable signs of toxicity. This pioneering MAP represents a significant advancement for the pulmonary gene therapy, enabling precise and effective delivery of aerosolized nanoparticles.