Abstract: There are provided herein, inter alia, complexes, compositions and methods for the delivery of therapeutic, diagnostic and imaging agents, including nucleic acid, into a cell. The complexes, compositions and methods may facilitate complexation, protection, delivery and release of oligonucleotides and polyanionic cargos into target cells, tissues, and organs both in vitro and in vivo.

Abstract: The introduction of tools to study, control or expand the inner-workings of algae has been slow to develop. Provided are embodiments of a molecular method based on guanidinium-rich molecular transporters (GR-MoTrs) for bringing molecular cargos into algal cells. The methods of the disclosure have been shown to work in wild-type algae that have an intact cell wall. Developed using Chlamydomonas reinhardtii, this method is also successful with less studied algae, including Neochloris oleoabundans and Scenedesmus dimorphus, thus providing a new and versatile tool for algal research and modification. The method of delivering a cargo compound to an algal cell comprises contacting an algal cell with a guanidinium-rich delivery vehicle comprising a guanidinium-rich molecular transporter (GR-MoTr) linked to a cargo compound desired to be delivered to the algal cell, whereby the guanidinium-rich molecular transporter can traverse the algal cell wall, thereby delivering the cargo compound to the algal cell.

Abstract: The introduction of tools to study, control or expand the inner-workings of algae has been slow to develop. Provided are embodiments of a molecular method based on guanidinium-rich molecular transporters (GR-MoTrs) for bringing molecular cargos into algal cells. The methods of the disclosure have been shown to work in wild-type algae that have an intact cell wall. Developed using Chlamydomonas reinhardtii, this method is also successful with less studied algae, including Neochloris oleoabundans and Scenedesmus dimorphus, thus providing a new and versatile tool for algal research and modification. The method of delivering a cargo compound to an algal cell comprises contacting an algal cell with a guanidinium-rich delivery vehicle comprising a guanidinium-rich molecular transporter (GR-MoTr) linked to a cargo compound desired to be delivered to the algal cell, whereby the guanidinium-rich molecular transporter can traverse the algal cell wall, thereby delivering the cargo compound to the algal cell.

Abstract: Co-oligomer compounds, complexes of the same with polyanions, such as siRNAs, and methods for using the same are provided. the delivery of polynucleotides, into a cell. The subject co-oligomers include at least a liphopilic monomer and at least a hydrophilic monomer (e.g., a guanidinium containing monomer). In some embodiments, the co-oligomer compounds are capable of complexing a siRNA of interest, thereby increasing the cell permeability of the siRNA, prior to release of the siRNA into the cell. In some embodiments, the subject method is a method of delivery a siRNA into a cell. In some embodiments, the subject method is a method of reducing expression of a protein target of a siRNA of interest. The subject co-oligomer/siRNA complexes may be formulated and administered to a subject to treat a condition resulting from expression of a protein target of the siRNA of interest.

Abstract: Embodiments of the present disclosure provide for prostratin analogs, bryostatin analogs, prodrugs of prostratin and prostratin analogs, methods of making prostratin analogs, and methods of making prodrugs of prostratin and prostratin analogs, methods of use of prostratin analogs, bryostatin analogs, and prodrugs thereof, and the like.

Abstract: Methods and materials for delivering biologically active molecules to cells in vitro or in vivo are provided. The methods and materials use carbon nanotubes or other hydrophobic particles, tubes and wires, functionalized with a linking group that is covalently bound to the nanotubes, or, alternatively, to the biologically active molecule, such as a protein. The biologically active molecule is preferably released from the nanotube when the complex has been taken up in an endosome.

Abstract: This invention provides compositions and methods for enhancing delivery of drugs and other agents across epithelial tissues, including the skin, gastrointestinal tract, pulmonary epithelium, ocular tissues and the like. The compositions and methods are also useful for delivery across endothelial tissues, including the blood brain barrier. The compositions and methods employ a delivery enhancing transporter that has sufficient guanidine or amidino sidechain moieties to enhance delivery of a compound conjugated to the reagent across one or more layers of the tissue, compared to the non-conjugated compound. The delivery-enhancing polymers include, for example, poly-arginine molecules that are preferably between about 6 and 25 residues in length.

Abstract: Biologically active compounds related to the bryostatin family of compounds, having simplified spacer domains and/or improved recognition domains are disclosed, including methods of preparing and utilizing the same.

Abstract: This invention provides compositions and methods for enhancing delivery of drugs and other agents across epithelial tissues, including into and across ocular tissues and the like. The compositions and methods are also useful for delivery across endothelial tissues, including the blood brain barrier. The compositions and methods employ a delivery enhancing transporter that has sufficient guanidino or amidino sidechain moieties to enhance delivery of a compound conjugated to the reagent across one or more layers of the tissue, compared to the non-conjugated compound. The delivery-enhancing polymers include, for example, poly-arginine molecules that are preferably between about 6 and 25 residues in length.

Abstract: Conjugates of a cargo molecule with a transporter molecule are disclosed, where the cargo molecule and the transporter molecule are linked covalently by a releasable linker. The cargo of the conjugate can be a biologically active agent or a reporter molecule. The transporter modulates the transport of the cargo across a biological barrier (e.g., a cell membrane) compared to the transport of the unconjugated cargo. Releasable linkers suitable for rapid and facile conjugation to various types of cargo and transporters are also disclosed, along with methods for using the linkers in the synthesis of conjugates.

Abstract: This invention provides compositions and methods for enhancing delivery of drugs and other agents across epithelial tissues, including the skin, gastrointestinal tract, pulmonary epithelium, ocular tissues and the like. The compositions and methods are also useful for delivery across endothelial tissues, including the blood brain barrier. The compositions and methods employ a delivery enhancing transporter that has sufficient guanidino or amidino sidechain moieties to enhance delivery of a compound conjugated to the reagent across one or more layers of the tissue, compared to the non-conjugated compound. The delivery-enhancing polymers include, for example, poly-arginine molecules that are preferably between about 6 and 25 residues in length.

Abstract: This invention concerns product and process to convert a hydroxyl group (bold in R3C—OH) in a tigliane-type compound to a hydrogen (bold in R3C—H) to obtain deoxytigliane-type compounds or structural or functional analogs thereof. The process has wide application particularly to produce specific biologically active compounds in quantity for use as pharmaceuticals. In particular the process can be used to convert phorbol to a 12-deoxytigliane (prostratin), which is a therapeutic lead for the treatment of AIDS. New compositions of matter are also disclosed.

Abstract: Biologically active compounds related to the bryostatin family of compounds, including methods of utilizing the same.

Abstract: This invention provides compositions and methods for enhancing delivery of drugs and other agents across epithelial tissues, including into and across ocular tissues and the like. The compositions and methods are also useful for delivery across endothelial tissues, including the blood brain barrier. The compositions and methods employ a delivery enhancing transporter that has sufficient guanidino or amidino sidechain moieties to enhance delivery of a compound conjugated to the reagent across one or more layers of the tissue, compared to the non-conjugated compound. The delivery-enhancing polymers include, for example, poly-arginine molecules that are preferably between about 6 and 25 residues in length.

Abstract: Methods and materials for delivering biologically active molecules to cells in vitro or in vivo are provided. The methods and materials use carbon nanotubes or other hydrophobic particles, tubes and wires, functionalized with a linking group that is covalently bound to the nanotubes, or, alternatively, to the biologically active molecule, such as a protein. The biologically active molecule is preferably released from the nanotube when the complex has been taken up in an endosome.

Abstract: This invention provides compositions and methods for enhancing delivery of drugs and other agents across epithelial tissues, including into and across ocular tissues and the like. The compositions and methods are also useful for delivery across endothelial tissues, including the blood brain barrier. The compositions and methods employ a delivery enhancing transporter that has sufficient guanidino or amidino sidechain moieties to enhance delivery of a compound conjugated to the reagent across one or more layers of the tissue, compared to the non-conjugated compound. The delivery-enhancing polymers include, for example, poly-arginine molecules that are preferably between about 6 and 25 residues in length (for example, SEQ ID NO:86).

Abstract: The present invention provides compositions and methods for enhancing transport of biologically active compounds across biological membranes and across and into animal epithelial or endothelial tissues. The composition includes a biologically active agent and a transport moiety. The transport moiety includes a structure selected from the group consisting of (ZYZ)nZ, (ZY)nZ, (ZYY)nZ and (ZYYY)nZ. Subunit “Z” is L-arginine or D-arginine, and subunit “Y” is an amino acid that does not comprise an amidino or guanidino moiety. Subscript “n” is an integer ranging from 2 to 10. The method for enhancing transport involves the administration of the aforementioned composition.

Abstract: Methods and materials for delivering biologically active molecules to cells in vitro or in vivo are provided. The methods and materials use carbon nanotubes or other hydrophobic particles, tubes and wires, functionalized with a linking group that is covalently bound to the nanotubes, or, alternatively, to the biologically active molecule, such as a protein. The biologically active molecule is preferably released from the nanotube when the complex has been taken up in an endosome.

Abstract: This invention concerns product and process to convert a hydroxyl group (bold in R3C—OH) in a tigliane-type compound to a hydrogen (bold in R3C—H) to obtain deoxytigliane-type compounds or structural or functional analogs thereof. The process has wide application particularly to produce specific biologically active compounds in quantity for use as pharmaceuticals. In particular the process can be used to convert phorbol to a 12-deoxytigliane (prostratin), which is a therapeutic lead for the treatment of AIDS. New compositions of matter are also disclosed.

Abstract: This invention concerns a process to convert a hydroxyl group (bold in R3C—OH) in a tigliane-type compound to a hydrogen (bold in R3C—H) to obtain deoxytigliane-type compounds or structural or functional analogs thereof. The process has wide application particularly to produce specific biologically active compounds in quantity for use as pharmaceuticals. In particular the process can be used to convert phorbol to a 12-deoxytigliane (prostrating which is a therapeutic lead for the treatment of AIDS. New compositions of matter are also disclosed.