1139results about "Special delivery" patented technology

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of a DMPK allele comprising a disease-associated-repeat. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Aspects of the disclosure relate to complexes and other aspects relate to formulations (e.g., aqueous, lyophilized forms) comprising such complexes comprising an oligonucleotide (e.g., useful for targeting DMPK) covalently linked to an antibody (e.g., anti-TfR1 antibody).

Aspects of the disclosure relate to complexes and other aspects relate to formulations (e.g., aqueous, lyophilized forms) comprising such complexes comprising an oligonucleotide (e.g., useful for targeting DMPK) covalently linked to an antibody (e.g., anti-TfR1 antibody).

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

The present disclosure relates to isolated nucleic acid molecules comprising at least two double-stranded inhibitory ribonucleic acid (RNA) molecules adapted to silence the same or different genes by RNA interference to enhance silence, thereby modulating gene expression.

The present disclosure, in some aspects, provides one or more biomarkers (e.g., plasma biomarkers or circulating biomarkers) for Facioscapulohumeral muscular dystrophy (FSHD). In some embodiments, a biomarker (e.g., plasma biomarkers or circulating biomarkers) described herein is regulated by DUX4. Methods (e.g., non-invasive methods) of using the biomarkers, e.g., for detection (e.g., early detection) and monitoring patient as well as treatment efficacy are also provided. The present disclosure, in other aspects, provides one or more biomarkers (e.g., transcriptome biomarkers) for Facioscapulohumeral muscular dystrophy (FSHD). In some embodiments, a biomarker (e.g., transcriptome biomarkers) described herein is regulated by DUX4. Methods of using the biomarkers, e.g., for detection (e.g., early detection) and monitoring patient as well as treatment efficacy are also provided.

Aspects of the disclosure relate to complexes and other aspects relate to formulations (e.g., aqueous, lyophilized forms) comprising such complexes comprising an oligonucleotide (e.g., useful for targeting DMPK) covalently linked to an antibody (e.g., anti-TfR1 antibody).

The present disclosure relates to cellular compositions that are modified to introduce a nucleic acid or vector expressing the same. Such compositions may be used to deliver nucleic acid to a target cell and treat disease such as cancer.

The invention relates to a key gene GqBurscon for wing development of a Qinghai grassland moth and application thereof. The key gene GqBurscon for the wing development of the Qinghai grassland caterpillar has a nucleotide sequence as shown in SEQ ID NO: 1. According to the dsRNA synthesized by the key gene GqBurscon for wing development of the Qinghai grass caterpillar, one chain of the dsRNA is the same as the sequence of SEQ ID NO: 1, and the other chain of the dsRNA is reversely complementary with the sequence of SEQ ID NO: 1. The key gene GqBurscon for the wing development of the Qinghai grassland is used for synthesizing dsRNA, the synthesized dsRNA is used for carrying out RNA interference on a target gene, the gene transcription level is knocked down, the gene is effectively silenced in chest, abdomen, wings and wing base tissues of male adult Qinghai grassland, the length and width of the wings are correspondingly reduced, the development of the wings is limited, and the gene transcription level is reduced. The flying capability is influenced, and the death is caused.

Described herein are muscle-specific targeting moieties and compositions including the muscle specific targeting motifs. Also described herein are uses of the muscle-specific targeting motifs and compositions including the muscle specific targeting moieties. In some embodiments, the muscle-specific targeting moieties and compositions including the muscle specific targeting moieties can be used to direct delivery of a cargo to a muscle cell.

The present invention relates to antisense oligonucleotides (AONs) that can mediate RNA editing by binding to a target RNA nucleic acid molecule, preferably an RNA transcript molecule, in a cell and recruiting an endogenous deaminating enzyme in the cell to deaminate a target adenosine in the target RNA molecule to an inosine. The target RNA molecule is a transcript molecule form the SLC10A1 gene that encodes the Na+ / Taurocholate Co-transporting Polypeptide (NTCP), and the target adenosine is the adenosine in the GAC codon coding for aspartic acid (D) at position 24 of the NTCP protein. The deamination of the adenosine changes the amino acid to a glycine (G). The RNA editing of the adenosine will result in a loss-of-function of the NTCP protein, which will result in lowered uptake of bile acids from the portal circulation into the liver, thereby lowering the risk of suffering from disorders related to bile accumulation in the liver.

The present disclosure provides linker compounds of Formula (I) or (II):pharmaceutically acceptable salts thereof, and related scaffolds and conjugates. The present disclosure also relates to uses of the linker compounds, scaffolds, and conjugates, e.g., in delivering nucleic acid and / or treating or preventing diseases.

To provide lipid-therapeutic nucleic acid compositions that encapsulate nucleic acids with high efficiency, have high drug:lipid ratios, protect the encapsulated nucleic acids from degradation and clearance in serum, are suitable for systemic delivery, and enable intracellular delivery of the encapsulated nucleic acids.SOLUTION: The invention provides lipids, or salts or isomers thereof. In the formula: R1 and R2 are each independently for each occurrence C10-C20 alkenyl; R3 is ω-aminoalkyl, ω-(substituted)aminoalkyl, or ω-thiophosphoalkyl; E is C(O)O; provided that if R3 is 2-(dimethylamino)ethyl then neither R1 nor R2 is linoleyl.SELECTED DRAWING: None

This disclosure relates to an siRNA-lipid conjugate of formula Y-L-(H)n. Y is an siRNA molecule. L is a linker covalently bonded to Y and H, each H is independently a hydrophobic chain comprising 5 to 50 carbon atoms, n is 1, 2, or 3, and linker L is bonded to the 3′ end of the sense strand of the siRNA.

Aspects of the present disclosure relate to conjugates comprising a muscle targeting agent covalently linked to a molecular payload. In some embodiments, the muscle targeting agent specifically binds to an internalized cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in mRNA expressed from a mutant DMD allele.

the present invention relates to peptides, in particular cell-penetrating peptides, having a first hydrophobic domain positioned at the C-terminus of the peptide and a second hydrophobic domain positioned at the N-terminus of the peptide, and to conjugates of such cell-penetrating peptides with a therapeutic molecule. The present invention further relates to use of such peptides or conjugates in methods of treatment or as a medicament, especially in the treatment of genetic disorders and in particular muscular dystrophies such as Duchenne muscular dystrophy.

Among other things, the present disclosure provides designed oligonucleotides and compositions thereof. In some embodiments, oligonucleotides and compositions of the present disclosure can provide high levels of adenosine editing. In some embodiments, oligonucleotides and compositions of the present disclosure are useful for treating various conditions, disorders or diseases, e.g., alpha-1 antitrypsin deficiency. In some embodiments, the present disclosure provides methods for treating various conditions, disorders or diseases that can benefit from adenosine editing.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits activity of a disease allele associated with muscle disease. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

Compositions and methods for introducing double-stranded breaks within the SERPINA1 gene are provided. Compositions and methods for reducing and eliminating mutant forms of α1-antitrypsin (AAT), such as seen in subjects having α1-antitrypsin deficiency (AATD), are provided.

The present disclosure provides a modified oligonucleotide sequence and its application. A series of siRNAs are designed based on the angiotensinogen (AGT) messenger ribonucleic acid (mRNA) sequence, and are alternately modified and modified using a specific set of modification templates. The results of cell and animal experiments show that some alternately modified and specifically template-modified oligonucleotide sequences can significantly inhibit the expression of the AGT gene, and can be used for developing drugs for treating related diseases such as hypertension.

Compositions and methods to prevent, inhibit or treat a disease or disorder associated with expression of APOE4 in a mammal are provided.

Disclosed herein are polynucleic acid molecules, pharmaceutical compositions, and methods of use for PRKAG2 antibody oligonucleotide conjugates (AOC).

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Oligomeric compounds (including those that are antisense agents or portions thereof) are provided that comprise a modified oligonucleotide having at least one modified internucleoside linking group.SOLUTION: By an oligomeric compound comprising a modified oligonucleotide consisting of 12 to 70 linked nucleosides linked via internucleoside linking groups, wherein at least one nucleoside comprises a modified sugar moiety and wherein at least one internucleoside linking group is a phosphodiester or phosphorothioate internucleoside linking group.SELECTED DRAWING: Figure 1

Provided is a method for controlling Monolepta hieroglyphica by means of using RNAi technology to reduce or silence the expression of a target gene combination in Monolepta hieroglyphica. The method selects MhCoPI gamma and Mhmi2 as target genes, designs a target sequence, and brings Monolepta hieroglyphica into contact with a corresponding dsRNA molecule, so as to inhibit the growth, development and reproduction of same and control the number of pests in the fields. Therefore, the control method is environment-friendly, efficient and safe.

RNAi agents, compositions comprising RNAi agents, and methods for inhibiting thymic stromal lymphopoietin (TSLP) gene expression are described. The TSLP RNAi agents and RNAi agent conjugates disclosed herein inhibit TSLP gene expression. Also described are pharmaceutical compositions comprising one or more TSLP RNAi agents, optionally together with one or more additional therapeutic agents. Delivery of the described TSLP RNAi agents to lung cells in vivo inhibits TSLP gene expression, which can provide therapeutic benefit to subjects, including human subjects, for the treatment of various diseases, including pulmonary inflammatory diseases such as asthma, including allergic asthma.

Some embodiments provide a method of treating skeletal muscular myopathy, e.g., Duchenne muscular dystrophy (DMD), with cardiosphere-derived cells (CDCs), wherein a therapeutically effective amount of CDCs is delivered to a targeted dystrophic skeletal muscle. Some embodiment enable delivery of a therapeutically effective amount of CDCs via intramuscular injection directly at a skeletal muscle or systemic administration, e.g., intravenous injection, in a single dose or multiple doses, to treat a targeted dystrophic skeletal muscle. Some embodiments provide a method for improving exercise capabilities in DMD patients. Additional embodiments relate to exosome mediated transfer of noncoding RNAs ameliorates Duchenne muscular dystrophy by restoring dystrophin in heart and skeletal muscle. Delivery of noncoding RNA species found in CDC-derived exosomes mimics the ability of CDCs and CDC-derived exosomes to increase dystrophin protein levels.

The present application relates to the field of medicine, in particular to oligonucleotide, viral vector and its application and RNAi drug preparation. The oligonucleotide is one or two of the nucleic acid sequences shown in SEQ ID NO: 1 to SEQ ID NO: 7; or the oligonucleotide with the nucleic acid sequence of the above-mentioned oligonucleotide is not less than 80% consistent. The present application finds that the RNAi drug can significantly reduce the expression of mutant COL8A2, can treat the corneal dystrophy that has occurred, and can prevent the occurrence of corneal dystrophy. It can be seen that the RNAi drug preparation of the present application can effectively treat and prevent the corneal dystrophy caused by COL8A2 mutation.