22 results about "Protein replacement therapy" patented technology

The invention provides an organic molecule cytoplasm delivery carrier as well as a preparation method and application thereof, the compound for cytoplasm delivery has the characteristic of fat-soluble aggregation, and can form electrostatic adsorption with small molecule protein goods such as RNase A (13.7 KDa), Trypsin (24KDa) and Saporin (32.8 KDa), medium molecule protein goods such as HRP (40KDa) and macromolecular protein goods such as beta-Gal (430KDa), so that the compound for cytoplasm delivery can be used for preparing a lipid-soluble protein carrier. And furthermore, transmembrane transportation is formed through the strong fat solubility property, so that the protection and intracellular delivery of carried protein molecules are realized. According to the delivery mechanism, cargo molecules can quickly penetrate through cell membranes, and carried protein molecules can enter cytoplasm to exert functions without release operation. Development of the organic molecule cytoplasm delivery carrier is expected to assist potential protein therapies with low bioavailability and off-target toxicity to complete clinical transformation, which is crucial to tumor therapy, gene therapy and the like requiring precise local administration.

Featured are the use of pharmaceutical compositions containing a CD40 antagonist or a CD154 antagonist for the treatment, reduction, and / or inhibition of an immune response, such as an anti-drug antibody response, following, e.g., protein replacement therapy or gene therapy.

Variants of coagulation factor VIII (FVIII) and expression cassettes encoding the FVIII variants thereof are described. A variant FVIII includes a glycoepitope of the FVIII protein including an N2118Q mutation. The N2118Q mutation can be combined with other mutations including a BDD-FVIII, N6, V3, RH, furin-cleavage site deletion. X10, K12, and / or F309S mutation to form additional FVIII variants. The FVIII variants with the N2118Q mutation and expression cassettes thereof can result in reduced immunogenicity of the resulting protein. When combined with other FVIII mutations, higher gene expression, increased secretion, increased stability, and higher FVIII functional activity can be achieved by the expressed FVIII variants. The variant FVIII and expression cassettes described here can be useful in protein replacement therapy and / or gene therapy for the treatment of hemophilia A.

The invention particularly discloses a medicine for treating hereditary liver diseases and application thereof, and relates to the technical field of gene therapy. The invention provides a lipid nanoparticle containing alanine glyoxylate aminotransferase mRNA (messenger Ribonucleic Acid). The lipid nanoparticle comprises an mRNA solution and a lipid mixed solution, the concentration ratio of the mRNA solution to the lipid mixed solution is 1: (20-120). According to the lipid nanoparticles provided by the invention, the problem that the parenchymal hepatic cell AGT enzyme of a patient with primary type 1 hyperoxaluria is deficient is solved, the AGT mRNA delivery efficiency is further improved, and the urine oxalate reduction effect of a protein replacement therapy is improved. The invention provides a theoretical basis and an experimental basis for developing a new treatment strategy, and has good clinical transformation and clinical application prospects.

The new alpharetrovirus-based particles are suitable for high efficiency of transiently transducing animal cells. e.g. human or murine cells, and which efficiently introduce coding and non-coding RNA contained in the alpharetrovirus-based particles into target cells The alpharetrovirus-based particles also provide for high efficiency of the activity and / or integrity of the RNA that is introduced into the animal cells, as the particles protect the incoming RNA from degradation during entry. The transferred RNA can be of non-coding nature (e.g. single guide (sg) RNA. short-hairpin (sh) RNA. micro RNA. or long non-coding (Inc) RNA. or the RNA may encode proteins or peptides. e.g. receptors. transcription factors. cellular enzymes, antigens for use in vaccination, gene / protein therapy and / or gene editing nucleases, recombinases and transposases.

This invention discloses the application of MYDGF in pharmaceuticals and medical devices for treating vascular intimal hyperplasia, belonging to the field of pharmaceutical technology. This invention utilizes MYDGF as a target in the preparation of products for protecting vascular function, and applies MYDGF in the preparation of drugs for treating vascular intimal hyperplasia, drugs for metabolic disorders related to vascular intimal hyperplasia, and medical devices for treating vascular intimal hyperplasia. This invention provides new candidate drugs and protein therapies for the clinical treatment of intimal hyperplasia.

The present application relates to natural ferritin, and particularly relates to an intracellular delivery system and application thereof. The system can effectively deliver various proteins into cells and maintain the biological activity thereof, and provides important technical support for the development of protein therapy with intracellular target as core. The method exhibits significant advantages in promoting intracellular protein transport, intracellular protein interaction research and protein level regulation. The delivery system has wide applicability, is simple to operate and safe and reliable, and becomes an important tool for future intracellular protein research and application.

The present application relates to the technical field of biotechnology, in particular to a hybridoma cell secreting KOD DNA polymerase monoclonal antibody, the monoclonal antibody and application thereof. The present application utilizes the hybridoma cell to produce the monoclonal antibody capable of specifically binding with KOD DNA polymerase, and the enzyme can be released under the condition of heat activation, so that the polymerization and exonuclease functions are restored. The monoclonal antibody of the present application can be widely applied to PCR amplification, DNA sequencing, gene cloning, protein expression, protein purification and other technologies in the field of molecular biology. The monoclonal antibody can also be used in diagnosis, treatment and prevention and other aspects in the field of biomedicine, such as used for detecting pathogenic microorganisms, tumor markers, gene mutations and the like, and used for gene therapy and protein therapy and the like for treating certain diseases, such as applied to the synthesis of cDNA second strand in the mRNA sequencing library construction process in the second-generation sequencing, so as to improve the sequencing quality and accuracy.

The present disclosure relates to an RNA-based protein replacement therapy for diseases characterised by an abnormality in, or deficiency of one or more proteins, or for which an abnormality in, or deficiency of one or more proteins is implicated In particular, the present disclosure relates to an RNA-based protein replacement therapy for diseases in which a protein deficiency affects vascular cells, and in particular, pulmonary endothelial and / or smooth muscle cells.

The invention encompasses novel ionizable lipids compounds and their use in lipid nanoparticles delivery systems that are useful in the delivery of nucleic acids to a mammalian subject that can be included for use, for example, as cancer vaccines, gene editing therapeutics, delivery of nucleic acid (e.g., mRNA) encoding antibodies, vaccines for infectious disease, and protein replacement therapeutics. Additionally, the invention encompasses compositions and therapeutics comprising the ionzable lipids in the lipid nanoparticles and the use of the composition and therapeutics for the preparation of a pharmaceutical composition, especially a vaccine, (e.g., for use in the prophylaxis or treatment of infectious diseases, tumor or cancer diseases, rare diseases, allergies, or autoimmune diseases). The invention encompasses methods of treatment or prophylaxis of the aforementioned diseases.

The invention discloses a high-stability mRNA construct as well as a preparation method and application thereof, and belongs to the technical field of gene therapy. The mRNA construct sequentially comprises a 5'untranslated region, an open reading frame for coding a target protein, a translation enhancement and stabilization element A7S, a 3 'untranslated region and a segmented Poly (A) tail from a 5'end to a 3' end. Wherein the segmented tail is composed of a plurality of adenylic acid fragments arranged alternately and a single cytosine spacer sequence, and a continuous adenylic acid sequence with the length larger than or equal to 20 nt is not included between the 3'untranslated region and the segmented Poly (A) tail. Through the synergistic effect of the specific segmented Poly (A) tail and the A7S element, the plasmid amplification instability is inhibited, and mRNA deadenylation degradation is delayed, so that the functional half-life period is prolonged. The construct and the pharmaceutical composition provided by the invention can be used for preparing gene therapy drugs such as long-acting protein replacement therapy.

The present invention relates generally to gene therapy for treating ailments that can affect vision such as retinal degeneration, retinal dystrophy, macular degeneration, macular dystrophy, ischemic retinopathies, and glaucoma. Embodiments include systems and treatments that use AAV-mediated gene therapy or non AAV-mediated DNA, mRNA, or protein therapy to target all retinal cells. An AAV virion can be introduced (e.g., via intravitreal or subretinal injection) into an eye of an individual, or systemically, to express a heterologous gene product such as BMI1 protein (B lymphoma Mo-MLV insertion region 1 homolog).

Proteins, nucleic acids encoding the proteins, compositions comprising the proteins, and methods are provided. The proteins have the ability to be self-targeted to ICAM-1 and, if desired, enzymatically-released at acidic pH. The ICAM-1-targeting peptides are provided as single copies or multiples repeats, and can be separated by linkers from the enzyme segment, from which the ICAM-1 targeting peptides can be released, if desired, at acidic pH. These fusion proteins enhance the activity of the enzyme segment within or liberated from the fusion protein, and provide increased recognition and targeting of diseased organs, transport from the bloodstream across the endothelium into said diseased organ, and intracellular uptake and lysosomal trafficking by cells in them, both in peripheral tissues and the central nervous system. Representative nucleotide and amino acid sequences of these fusion proteins, as well as in vitro, cellular, and in vivo animal data are provided. The described proteins can be used as a protein therapy, a gene therapy, or an implanted cell therapy.

An IL10RA mutant protein according to one aspect of the present invention solves the issue of commercial IL10RA proteins being impossible to purify, and is a protein with improved purification efficiency. The IL10RA mutant protein is expressed at a similar level similar to the wild-type IL10RA protein, is normally located in the cell membrane, and exhibits the same level of anti-inflammatory signaling activity as the wild-type protein upon IL-10 stimulation, and thus can be effectively used as a protein replacement therapy for the treatment of inflammatory diseases.

The invention encompasses novel ionizable lipids compounds and their use in lipid nanoparticles delivery systems that are useful in the delivery of nucleic acids to a mammalian subject that can be included for use, for example, as cancer vaccines, gene editing therapeutics, delivery of nucleic acid (e.g., mRNA) encoding antibodies, vaccines for infectious disease, and protein replacement therapeutics. Additionally, the invention encompasses compositions and therapeutics comprising the ionizable lipids in the lipid nanoparticles and the use of the composition and therapeutics for the preparation of a pharmaceutical composition, especially a vaccine, (e.g., for use in the prophylaxis or treatment of infectious diseases, tumor or cancer diseases, rare diseases, allergies, or autoimmune diseases). The invention encompasses methods of treatment or prophylaxis of the aforementioned diseases.

Provided are methods and compositions for expressing a functional dystrophin protein or a functional fragment thereof in a subject. The method can include administering a nucleic acid encoding the dystrophin protein to the subject, administering a sonoactive agent to the subject, and applying ultrasound energy the cell. Also provided are use of a nucleic acid encoding a functional dystrophin protein and a sonoactive agent in a method of treating a subject having a dystrophinopathy disorder requiring a dystrophin gene therapy or a dystrophin protein replacement therapy.

Provided are methods and compositions for expressing a functional dystrophin protein or a functional fragment thereof in a subject. The method can include administering a nucleic acid encoding the dystrophin protein to the subject, administering a sonoactive agent to the subject, and applying ultrasound energy the cell. Also provided are use of a nucleic acid encoding a functional dystrophin protein and a sonoactive agent in a method of treating a subject having a dystrophinopathy disorder requiring a dystrophin gene therapy or a dystrophin protein replacement therapy.

The present invention relates to the use of glutamine synthetase as a protein therapy (such as enzyme replacement protein therapy) for the treatment of hyperammonemia. In particular the invention relates to the systemic administration of glutamine synthetase. The glutamine synthetase may be provided in conjugated or fusion form, to increase its half-life in the circulation. Also provided is a pharmaceutical composition comprising glutamine synthetase. The invention also relates to the uses, methods and compositions involving a combination of the glutamine synthetase protein and an ammonia lowering agent, such as a nitrogen scavenger.

The present invention provides a method for providing modified mRNAs of reduced immunogenicity and / or immunostimulatory capacity for use in protein replacement therapy. The invention further provides modified mRNAs and pharmaceutical compositions comprising the modified mRNAs according to the invention for use in protein replacement therapy.

The application discloses a high-stability mRNA construct and a preparation method and application thereof, and belongs to the technical field of gene therapy. The mRNA construct comprises, from 5' end to 3' end, a 5' untranslated region, an open reading frame coding a target protein, a translation enhancement and stabilization element A7S, a 3' untranslated region and a segmented Poly(A) tail. The segmented tail is composed of multiple alternating adenosine fragments and single cytosine spacer sequences, and there is no continuous adenosine sequence with a length of greater than or equal to 20 nt between the 3' untranslated region and the segmented Poly(A) tail. The application inhibits plasmid amplification instability and delays mRNA adenosine degradation to prolong the functional half-life through the synergistic effect of the specific segmented Poly(A) tail and the A7S element. The construct and the pharmaceutical composition provided by the application can be used for preparing long-acting gene therapy drugs such as protein replacement therapy.

The application belongs to the technical field of biological medicine, and particularly relates to a SaRNA subgenomic promoter mutant, a mutation method and application thereof. The application obtains a series of promoter mutants with significantly improved expression efficiency by site-directed mutagenesis on the SaRNA subgenomic promoter. Compared with the wild-type promoter, the mutant significantly enhances the expression level of the downstream gene at the cell level and in the animal body. The SaRNA constructed based on the mutant can achieve the same or stronger protein expression effect at a lower dose, and has a wide application prospect in the fields of infectious disease prevention, tumor immunotherapy and protein replacement therapy.