12 results about "Protein replacement therapy" patented technology

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 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 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).

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 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.