The present invention provides a modified RNAi agent comprising a sense strand and an antisense strand, wherein the antisense strand targets an HBV mRNA; all of the nucleotide sugars of the RNAi agent are 2′-modified; and at least one of the sense and antisense strands is conjugated to at least one targeting ligand that comprises two or more building blocks connected to a biantennary or triantennary branched linker, optionally via one or more linking groups.

Provided herein are tethered extracellular vesicles and methods of making tethered extracellular vesicles.

Disclosed herein are methods and compositions engineered to modulate EphA2, including novel peptides with unexpectedly high specificity and binding affinity. The compositions described herein can be attenuated to treat subjects suffering from diseases and/or conditions.

The present embodiments provide methods, compounds, and compositions for treating, preventing, or ameliorating a disease associated with excess growth hormone using antisense compounds or oligonucleotides targeted to growth hormone receptor (GHR).

The poly(pro-drug) material includes one or more alternating therapeutic compounds and biodegradable hydrocarbyl groups. The therapeutic compounds and biodegradable hydrocarbyl groups are separated by cleavable linker compounds. The therapeutic compounds, such as estrogen, curcumin, and fingolimod, include a plurality of substitutable functional groups that provide reaction sites for complexing with the cleavable linkers and in turn one or more polymers, such that the poly(pro-drug) material ends up composed of the therapeutic compound itself. In aqueous media and at physiological temperature and pH, the poly(pro-drug) materials degrade to release the therapeutic compounds from the material with a zero-order release profile, Advantageously, the poly(pro-drug) materials release the therapeutic compounds on time scales of years. The poly(pro-drug) materials also exhibit reduced to allow for prolonged implantation within a patient. These materials are enticing for a myriad of biomedical applications, including veterinary medicine, cancer treatments, birth control, and hormone replacement therapy.

The poly(pro-drug) material includes one or more alternating therapeutic compounds and biodegradable hydrocarbyl groups. The therapeutic compounds and biodegradable hydrocarbyl groups are separated by cleavable linker compounds. The therapeutic compounds, such as estrogen, curcumin, and fingolimod, include a plurality of substitutable functional groups that provide reaction sites for complexing with the cleavable linkers and in turn one or more polymers, such that the poly(pro-drug) material ends up composed of the therapeutic compound itself. In aqueous media and at physiological temperature and pH, the poly(pro-drug) materials degrade to release the therapeutic compounds from the material with a zero-order release profile, Advantageously, the poly(pro-drug) materials release the therapeutic compounds on time scales of years. The poly(pro-drug) materials also exhibit reduced to allow for prolonged implantation within a patient. These materials are enticing for a myriad of biomedical applications, including veterinary medicine, cancer treatments, birth control, and hormone replacement therapy.

The present invention relates to the fields of molecular medicine and targeted delivery of therapeutic or diagnostic agents to cells outside the vascular system and into the parenchymal tissue of organs within the body. More specifically, the present invention relates to the methods used to identify membrane receptors or transporters capable of carrying cargo specifically targeted to the parenchymal tissue of the brain and to in vivo enrichment methods for selecting peptides that are transported across the blood-brain barrier (“BBB”), or analogously, across other membrane containing organs or structures, such as liver, spleen, kidney and tumors.

The present invention relates to the fields of molecular medicine and targeted delivery of therapeutic or diagnostic agents to cells outside the vascular system and into the parenchymal tissue of organs within the body. More specifically, the present invention relates to the methods used to identify membrane receptors or transporters capable of carrying cargo specifically targeted to the parenchymal tissue of the brain and to in vivo enrichment methods for selecting peptides that are transported across the blood-brain barrier (“BBB”), or analogously, across other membrane containing organs or structures, such as liver, spleen, kidney and tumors.

The present invention relates to products and compositions and their uses. In particular the invention relates to nucleic acid products that interfere with the TMPRSS6 gene expression or inhibits its expression and therapeutic uses such as for the treatment of hemochromatosis, porphyria and blood disorders such as β-thalassemias, sickle cell disease and transfusional iron overload or myelodysplastic syndrome.

The present invention provides a phosphorothioate-modified oligonucleotide comprising a structure shown below:

##STR00001##

The present invention also provides a phosphorothioate-modified oligonucleotide comprising a structure having formula (CIII):

##STR00002##