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.

Essentially non-aqueous liquid pharmaceutical formulations are formed by mixing at least one pharmaceutically active ingredient and at least one other compound capable of interacting with the active pharmaceutical ingredient through non-covalent interactions to form a low-temperature transition mixture. The stable liquid formulations are readily obtained, even with drugs that are poorly soluble and/or unstable in water.

The present invention provides targeting lipids of structure
L.sup.100-linker-L.sup.101  (CI),
where L.sup.100 is a lipid, lipophile, alkyl, alkenyl or alkynyl, L.sup.101 is a ligand or —CH.sub.2CH.sub.2(OCH.sub.2CH.sub.2).sub.pO(CH.sub.2).sub.qCH.sub.2-ligand, p is 1-1000, and q is 1-20. In addition, the invention provides compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo.

An siRNA conjugate having a structure as represented by formula (1) for inhibiting hepatitis B vims gene expression, comprising siRNA and a conjugated group, wherein the sense strand of the siRNA comprises a nucleotide sequence 1, and the antisense strand comprises a nucleotide sequence 2; the nucleotide sequence 1 and the nucleotide sequence 2 are, at least in part, reversely complementary to form a double-stranded region; the nucleotide sequence 1 and SEQ ID NO: 1 are equal in length and differ by no more than three nucleotides; the nucleotide sequence 2 and SEQ ID NO: 2 are equal in length and differ by no more than three nucleotides. The siRNA conjugate can specifically target liver cells and effectively solve the problem of siRNA delivery in vivo, and shows excellent activity and low toxicity to inhibit HBV gene expression while maintaining high stability of siRNA.

The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the SERPINF2 gene. The invention also relates to methods of using such RNAi agents to inhibit expression of a SERPINF2 gene and to methods of preventing and treating a SERPINF2-associated disorder, e.g., a disorder associated with thrombosis.

The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the SERPINF2 gene. The invention also relates to methods of using such RNAi agents to inhibit expression of a SERPINF2 gene and to methods of preventing and treating a SERPINF2-associated disorder, e.g., a disorder associated with thrombosis.

An amphiphilic block copolymer having any one of the formulas S-[B]-H, S-[B]-H(D), D-[B]-H, S-B(D)-H, S-[B]-H-[B]-S, S-[B]-H(D)-[B]-S, D-[B]-H-[B]-S, D-[B]-H-[B]-D, S-B(D)-H-[B]-S or S-B(D)-H-B(D)-S; wherein S is a hydrophilic surface stabilizing group; B is a spacer group; H is a hydrophobic polymer or oligomer; D is a drug molecule; ( ) denotes that the group is bonded directly or indirectly as a side chain or as part of a side chain group to the adjacent group; [ ] denotes that the group is optional; and - denotes that each of the adjacent S, B, H or D are linked directly to one another or indirectly to one another via a linker group.

An amphiphilic block copolymer having any one of the formulas S-[B]-H, S-[B]-H(D), D-[B]-H, S-B(D)-H, S-[B]-H-[B]-S, S-[B]-H(D)-[B]-S, D-[B]-H-[B]-S, D-[B]-H-[B]-D, S-B(D)-H-[B]-S or S-B(D)-H-B(D)-S; wherein S is a hydrophilic surface stabilizing group; B is a spacer group; H is a hydrophobic polymer or oligomer; D is a drug molecule; ( ) denotes that the group is bonded directly or indirectly as a side chain or as part of a side chain group to the adjacent group; [ ] denotes that the group is optional; and - denotes that each of the adjacent S, B, H or D are linked directly to one another or indirectly to one another via a linker group.

Provided herein are compositions and nanocarriers comprising linear-dendritic telodendrimers (TD) containing riboflavin. The nanocarriers and compositions have desirable loading properties and stabilized structure and can be used for efficient in vivo delivery.