The current invention relates to an effector moiety capable of inducing an intracellular effect when present inside a mammalian cell, the effector moiety comprising a payload conjugated with at least one saponin. The invention also relates to an antibody-drug conjugate comprising the effector moiety according to the invention, or a ligand-drug conjugate comprising the effector moiety of the invention, the effector moiety comprising covalently coupled saponin. The invention also relates to a therapeutic combination comprising: (a) the effector moiety of the invention, comprising at least one saponin, and optionally a pharmaceutically acceptable excipient; and (b) an antibody-drug conjugate or a ligand-drug conjugate, and optionally a pharmaceutically acceptable excipient. Further, the invention relates to a pharmaceutical composition comprising the effector moiety of the invention or the antibody-drug conjugate of the invention or the ligand-drug conjugate of the invention, comprising at least one saponin covalently linked to the effector molecule, and optionally a pharmaceutically acceptable excipient. The invention also relates to the effector moiety of the invention or the antibody-drug conjugate of the invention or the therapeutic combination of the invention or the ligand-drug conjugate of the invention or the pharmaceutical composition of the invention, for use as a medicament. Finally, the invention also relates to the effector moiety of the invention or the antibody-drug conjugate of the invention or the therapeutic combination of the invention or the ligand-drug conjugate of the invention or the pharmaceutical composition of the invention, for use in the treatment or prevention of a cancer or an autoimmune disease.

The disclosure provides methods for treating or limiting development age-related macular degeneration, comprising (a) a GPR143 receptor agonist, including but not limited to L-DOPA, L-DOPA analogues, or a pharmaceutically acceptable salt thereof, and (b) melatonin, a melatonin analogue, or a pharmaceutically acceptable salt thereof, and related compositions.

A system for delivery of drugs, and especially genetic drugs such as siRNA or antisense oligonucleotides (ASO) across biological membranes is provided. It comprises a trans-membrane delivery moiety, energized by the membrane internal electrical field, and a redox-sensitive disulfide moiety, designed to be reduced at the cytoplasm, thus releasing the cargo drug to exert its pharmaceutical effects at its target sites.

This disclosure relates to novel SNCA targeting sequences. Novel SNCA targeting oligonucleotides for the treatment of neurodegenerative diseases are also provided.

The present invention provides, among other things, compositions and methods of formulating nucleic acid-containing nanoparticles comprising no more than three distinct lipids components, one distinct lipid component being a sterol-based cationic lipid. In some embodiments, the present invention provides compositions and methods in which the lipid nanoparticles further comprise helper lipids and PEG-modified lipids. The resulting formulation comprises a high encapsulation percentage for nucleic acids.

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

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

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This application discloses prodrug-based thermosensitive gel (“ProGel”) comprised of conjugates of dmg molecules with water-soluble polymeric carriers, which are capable of controlled release of the dmg molecules into the tissue of a subject. Use of the ProGel-Drug conjugates for treatment of various diseases or disorders and methods of preparing them are also disclosed.

The present disclosure relates to a toll-like receptor 7/8 agonist-cholesterol complex comprising: a cholesterol; and a toll-like receptor 7/8 agonist, wherein the cholesterol is linked to an active site of the toll-like receptor 7/8 agonist.

In an embodiment of the invention, a composition for treating a cell population comprises an Affinity Medicant Conjugate (AMC). The medicant moiety can be a toxin including an acylfulvene or a drug moiety. The affinity moiety can be an antibody, a binding protein, a steroid, a lipid, a growth factor, a protein, a peptide or non peptidic. The affinity moiety can be covalently bound to the medicant via a linker. Novel linkers that can be directed to cysteine, arginine or lysine residues based on solution pH allow greater flexibility in preserving and/or generating specific epitopes in the AMC.

The present disclosure relates to use of heparin analogues as inhibitors of proprotein convertase subtilisin-like/kexin type 9 (PCSK9) for the treatment of lipoprotein metabolism disorders.