60 results about "SOD1" patented technology

Compositions and methods relating to paraoxonase fusion polypeptides are disclosed. In some aspects, the fusions are bispecific molecules that include a first biologically active polypeptide linked amino-terminal to a biologically active paraoxonase, wherein the first biologically active polypeptide is a DNase, an RNase, a SOD1, a CTLA-4 extracellular domain, a CD40 extracellular domain, or a polypeptide that specifically binds and neutralizes an inflammatory cytokine. Bispecific fusions may further include a second biologically active polypeptide (e.g., a dimerizing or FcRn-binding domain) linked carboxyl-terminal to the first biologically active polypeptide and amino-terminal to the paraoxonase. In other aspects, a fusion polypeptide includes a biologically active paraoxonase linked carboxyl-terminal or amino-terminal to a dimerizing or FcRn-binding domain. Also disclosed are dimeric proteins comprising first and second paraoxonase fusion polypeptides as disclosed herein. The fusion polypeptides and dimeric proteins are useful in methods for therapy.

In some aspects, the disclosure relates to compositions and methods useful for inhibiting SOD1 expression in cells (e.g., cells of a subject). In some embodiments, the disclosure describes isolated nucleic acids engineered to express an inhibitory nucleic acid targeting endogenous SOD1 and an mRNA encoding a hardened SOD1 protein. In some embodiments, compositions and methods described by the disclosure are useful for treating Amyotrophic Lateral Sclerosis (ALS) in a subject.

Described herein are methods of inhibiting an allele that contains a mutation in a cell (e.g., treating a subject with an allele that contains a mutation). The method includes delivering to the cell an antisense oligonucleotide that targets a variant allele that is in cis with the mutation (e.g., the mutation is a gain of function mutation or a dominant negative mutation), wherein the cell or subject is heterozygous for the target variant, and the antisense molecule is effective at knocking down expression the target variant allele (e.g., effective at preventing, treating, or ameliorating at least one symptom associated with the mutation). Also described herein are methods of haplotyping a cell or subject, and antisense oligonucleotides that target mutant superoxide dismutase 1 (SOD1) and other genes.

The present application relates to siRNA and oligonucleotide agents for use in the prevention or treatment of SOD1-related neurodegenerative diseases or conditions, such as amyotrophic lateral sclerosis, ALS. The oligonucleotide agent comprises a double-stranded targeting oligonucleotide (siRNA) and a non-targeting single-stranded oligonucleotide (ACO), wherein the siRNA targets the mRNA region of the target gene SOD1.

Provided herein are compositions, systems, and methods comprising effector proteins for treating spinal muscular atrophy. These effector proteins may be characterized as CRISPRassociated (Cas) proteins. Various compositions, systems, and methods of the present disclosure may leverage the activities of these effector proteins for the modification of the SOD1 gene.

The invention relates to the technical field of gene engineering, and discloses a construction method of a humanized zebrafish amyotrophic lateral sclerosis model. Comprising the following steps: constructing a knock-in donor plasmid containing a left homologous arm sequence, a human mutation SOD1 gene sequence and a 3 'UTR sequence of a zebra fish sod1 gene, wherein the left homologous arm contains a target sequence of sgRNA and a second exon sequence of the zebra fish sod1 gene; the method comprises the following steps: knocking in a donor plasmid and Cas9 protein into sgRNA of which the target sequence is as shown in SEQ ID NO: 1, injecting the donor plasmid and the Cas9 protein into fertilized eggs of zebra fish, culturing into adult fish, and screening out a strain of which the human mutation SOD1 gene is correctly inserted into a zebra fish genome. According to the invention, sgRNA with a specific sequence is matched with a corresponding method, so that the human mutated SOD1 gene can be inserted into a zebra fish genome, the expression of the human mutated SOD1 is realized, the expression of an endogenous sod1 gene in the zebra fish is destroyed, and the construction of a humanized ALS model is realized for the first time.

Provided herein are SOD1 RNAi agents and compositions comprising a SOD1 RNAi agent. Also provided herein are methods of using the SOD1 RNAi agents or compositions comprising a SOD1 RNAi agent in reducing SOD1 expression and / or treating SOD1-mediated neurological disease.

SnRNA systems targeting SOD1 RNA sequences are disclosed herein. Further disclosed are methods of treating Amyotrophic Lateral Sclerosis.

In some aspects, the disclosure relates to compositions and methods useful for inhibiting SOD1 expression in cells (e.g., cells of a subject). In some embodiments, the disclosure describes isolated nucleic acids engineered to express an inhibitory nucleic acid targeting endogenous SOD1 and an mRNA encoding a hardened SOD1 protein. In some embodiments, compositions and methods described by the disclosure are useful for treating Amyotrophic Lateral Sclerosis (ALS) in a subject.

The invention discloses a construction method and application of a zebra fish model. The construction method comprises the following steps: taking zebra fish as a model animal, and obtaining a zebra fish model by knocking out a sod1 gene in the zebra fish and / or expressing a human source sod1 gene mutant in the zebra fish; wherein the serial number of the sod1 gene in the zebra fish in an Ensepbl database is ENSDARG00000043848, and the nucleotide sequence of the human source sod1 gene mutant is as shown in SEQ ID NO. 1. The zebrafish can be used for the function research of the sod1 gene in the zebrafish, the function research of the human-derived sod1 gene mutant, the pathological research of amyotrophic lateral sclerosis and the screening of amyotrophic lateral sclerosis resisting drugs.

The present invention relates to small interfering RNA (siRNA) molecules against the SOD1 gene, adeno-associated viral (AAV) vectors encoding siRNA molecules and methods for treating amyotrophic lateral sclerosis (ALS) using the siRNA molecules and AAV vectors.

To provide compositions and methods for treating and preventing amyotrophic lateral sclerosis.SOLUTION: Dosage regimens for SOD1-targeting antisense oligonucleotides and salts thereof are provided. These dosage regimens find use in the treatment of subjects having or at risk of developing amyotrophic lateral sclerosis. In a first aspect, the disclosure provides a method of treating or preventing amyotrophic lateral sclerosis associated with a mutation in the human superoxide dismutase 1 (SOD1) gene in a human subject in need thereof.SELECTED DRAWING: None

Antibody or binding fragment thereof, fusion protein, or pharmaceutical composition directed against misfolded SOD1 epitope, or nucleic acid encoding the antibody or binding fragment thereof, fusion protein, or pharmaceutical composition, are described. Also provided are methods for using and manufacturing such antibody or binding fragment thereof, fusion protein, nucleic acid, or pharmaceutical composition, as well as methods of their use for treating a disorder in a human subject in need thereof.

Aspects of the disclosure relate to compositions and methods for reducing expression or activity of superoxide dismutase 1 (SOD1) in a cell or subject. In some embodiments, the compositions, such as nucleic acid and viral vectors, comprise artificial microRNAs (amiRNAs) having a SOD 1 -targeting sequence positioned within a microRNA scaffold. In some embodiments, the compositions further comprise a human SMN1 promoter. In some aspects, the methods comprise administering a composition of the disclosure to a subject, for example a subject having amyotrophic lateral sclerosis (ALS).

The disclosure features compositions and methods for the treatment of disorders associated with expression of wild-type or mutant superoxide dismutase 1 (SOD1) RNA transcripts, that can lead to a 5 pathological phenotype. Disclosed herein are inhibitory RNA constructs that suppress the expression of SOD1, as well as viral vectors, such as adeno-associated viral vectors, encoding such inhibitory RNA molecules.

Provided are a modified double-stranded RNAi molecule and a use thereof. In particular, the present application relates to a double-stranded RNAi molecule for inhibiting sod1 gene expression, comprising a sense strand and an antisense strand which are complementary to form a double-stranded region, wherein the sense strand or the antisense strand comprises 15-25 nucleotides or consists of 15-25 nucleotides, and at least one nucleotide in the double-stranded RNAi agent is modified. Also provided is a use of the modified double-stranded RNAi molecule, which has high inhibitory activity and stability, also has high nervous system permeability, and can be used for treating and / or preventing sod1 gene-mediated diseases.

To provide compositions and methods useful for inhibiting SOD1 expression in cells (e.g., cells of a subject).SOLUTION: In some embodiments, the disclosure describes isolated nucleic acids engineered to express an inhibitory nucleic acid targeting endogenous SOD1 and an mRNA encoding a reinforced SOD1 protein. In some embodiments, compositions and methods described in the disclosure are useful for treating Amyotrophic Lateral Sclerosis (ALS) in a subject.SELECTED DRAWING: Figure 1

Abstract Dosage regimens for SOD1-targeting antisense oligonucleotides, and salts thereof, are provided. These dosage regimens find use in the treatment of subjects having or at risk of developing amyotrophic lateral sclerosis. Abstract 20 26 20 53 14 06 J ul 2 02 6 A b s t r a c t 2 0 2 6 2 0 5 3 1 4 0 6 J u l 2 0 2 6

Dosing regimens of SOD1 targeting antisense oligonucleotides and salts thereof are provided. These dosing regimens are useful for treating a subject suffering from or at risk of developing amyotrophic lateral sclerosis.

The invention relates to the technical field of protein, in particular to a preparation method and application of deep-deep-derived grease-resistant low-temperature superoxide dismutase SOD1. Through rational design or high-throughput screening, the SOD1 variant which keeps high activity in a grease environment and is sensitive to temperature is obtained, and the sequence is as shown in SEQ ID NO: 6. The enzyme can be widely applied to the technical fields of food preservation, skin care products, grease oxidation resistance and low-temperature biology, and the key defects of existing SOD1 in industrial application are overcome.

The present invention relates to an improved beta amyloid oligomer (A [beta] Os) specific binding antibody. Specifically, the invention relates to an improved form of a W20 antibody, the affinity of the improved form of the W20 antibody with AbetaOs is remarkably improved compared with that of the W20 antibody, Abeta aggregation and AbetaOs-induced nerve cell toxicity can be more remarkably inhibited, the cognitive and memory functions of an Alzheimer disease model mouse are more effectively improved, and pathological changes in the brain of the mouse are reduced. The antibody in an improved form can be specifically combined with oligomers of beta amyloid protein, alpha-synuclein, mHTT and SOD1, inhibits aggregation and cytotoxicity of each amyloid protein, has better potential for treating various amyloid protein diseases such as Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and the like compared with a W20 antibody, and can be used for preparing an antibody for treating various amyloid protein diseases such as Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. The improved antibody can be specifically combined with a strong-toxicity amyloid protein oligomer A beta o * 3F and has a better AD diagnosis value, and the amino acid sequence of the W20 antibody is as shown in SEQ ID No.1.

The present invention is directed to a pharmaceutical composition and method for treating a subj ect diagnosed amyotrophic lateral sclerosis (ALS) with a pharmaceutical composition containing dissolved or dispersed therein a SOD1 and / or TDP-43 aggregation- inhibiting amount of a rose bengal (RB) compound that is a pharmaceutically acceptable salt of RB, RB lactone, a RB amide, an aromatic RB derivative, wherein the aromatic derivative is an ester or amide formed from an alcohol or monosubstituted amine having a 5 - or 6 -membered aromatic ring, or a 5, 6 - or 6, 6 - fused aromatic ring system that contains 0, 1, or 2 hetero ring atoms that are independently nitrogen, oxygen or sulfur. This treatment method is typically repeated a plurality of times or until the subj ect no longer needs it.

Aspects of this disclosure provide compounds, compositions, and methods for regulating the expression or activity of superoxide dismutase 1 (SOD1). In some aspects, the compounds, compositions, and methods of this disclosure can be used to reduce the expression of SOD1 mRNA in cells or animals. In some aspects, the compounds, compositions, and methods of this disclosure can be used to reduce the expression of SOD1 protein in cells or animals. In certain embodiments, the animal has a CNS-related disease, disorder, or condition.

This invention relates to the field of bioactive peptide technology, and discloses a tetrapeptide with cognitive-improving function and its applications. The primary amino acid sequence of the tetrapeptide is Lys-Gly-Phe-Pro, and its molecular weight is 489.2587 Da. The tetrapeptide of this invention can be chemically synthesized or directionally prepared from sea cucumber protease hydrolysates. The tetrapeptide of this invention exhibits cognitive-improving activity, mainly through inhibiting GABA. B The expression of R activates the cAMP / PKA / CREB signaling pathway, promotes the release of the inhibitory neurotransmitter GABA, reduces oxidative stress damage, increases the gene expression of neurotrophic factors Bdnf and Nt3, and significantly upregulates the gene expression of antioxidant enzymes Sod1 and Gpx1, thereby exerting a neuroprotective effect and improving age-induced cognitive impairment.

The present invention is directed to a pharmaceutical composition and method for treating a subject diagnosed amyotrophic lateral sclerosis (ALS) with a pharmaceutical composition containing dissolved or dispersed therein a SOD1 and / or TDP-43 aggregation-inhibiting amount of a rose bengal (RB) compound that is a pharmaceutically acceptable salt of RB, RB lactone, a RB amide, an aromatic RB derivative, wherein the aromatic derivative is an ester or amide formed from an alcohol or monosubstituted amine having a 5- or 6-membered aromatic ring, or a 5,6- or 6,6-fused aromatic ring system that contains 0, 1, or 2 hetero ring atoms that are independently nitrogen, oxygen or sulfur. This treatment method is typically repeated a plurality of times or until the subject no longer needs it.

Use of a protein polymer in the treatment of amyotrophic lateral sclerosis. The protein polymer is obtained by stimulating and subsequently lysing mesenchymal stem cells, followed by isolation and purification. In SOD1 mutant mouse experiments, the protein polymer can significantly increase the number of motor neurons in the spinal anterior horn, ameliorate muscle atrophy, improve the motor ability of mice, and prolong the survival time of mice. In clinical trials, the protein polymer exhibits the effect of blocking the progression of amyotrophic lateral sclerosis, can reduce the concentration of TDP-43 protein in cerebrospinal fluid, and can increase the concentration of TDP-43 protein in serum.

The present disclosure features compositions and methods for treating a condition associated with the expression of a wild-type or mutant superoxide dismutase 1 (SOD1) RNA transcript, which can result in a pathological phenotype. Disclosed herein are inhibitory RNA constructs that inhibit the expression of SOD1, as well as viral vectors, such as adeno-associated viral vectors, encoding such inhibitory RNA molecules.

The present invention relates to a use of a novel compound, for preventing, improving or treating amyotrophic lateral sclerosis (ALS), wherein the present inventors have found that SOD1 aggregation is one of the important causes of ALS, and have proposed the possibility that WT-SOD1 aggregation, caused by suppressing the regulation of intracellular stress or TDP-43, may be a cause of sALS. In addition, the present inventors have discovered the novel compound PRG-A-01(SLC-B036) as a SOD1 aggregation and misfolding inhibitor.

To solve the problem of the lack of biomarkers that facilitate early diagnosis, demonstrate target binding, monitor disease progression, and / or can serve as surrogate end points for evaluating the efficacy of treatment.SOLUTION: Provided is a novel high-sensitivity method for assaying misfolded SOD1 in a body fluid of a subject, particularly in cerebrospinal fluid. The method is based on a novel high-sensitivity immunoassay utilizing a unique epitope of SOD1 and a corresponding anti-SOD1 antibody. In addition, a kit containing the components of an immunoassay is provided.SELECTED DRAWING: None

Aspects of the disclosure relate to compositions and methods for reducing expression or activity of superoxide dismutase 1 (SOD1) in a cell or subject. In some embodiments, the compositions, such as nucleic acid and viral vectors, comprise artificial microRNAs (amiRNAs) having a SOD1-targeting sequence positioned within a microRNA scaffold. In some embodiments, the compositions further comprise a human SMN1 promoter. In some aspects, the methods comprise administering a composition of the disclosure to a subject, for example a subject having amyotrophic lateral sclerosis (ALS).