Abstract: The invention relates to novel fluorescent dyes based on the following pyrenyloxy sulfonamide structure: wherein R1 is a leash joined to the pyrenyloxy group via an ether link containing generally a reactive functional group such as, activated carbonate, activated ester, amino group, azide or alkyne for conjugation with biomolecules; R2 and R3 are hydrogen atoms, or short alkyl chains, or cyclic rings with or without heteroatoms such as nitrogen, oxygen, sulfur, phosphorus. The spectral properties of the fluorescent dyes are sufficiently different in wave-lengths and intensity from fluorescein as to permit simultaneous use of fluorescein and/or more other fluorescent dyes with minimum interference and to avoid interference from endogenous green fluorescent protein in biological system. The dyes are non-ionic to facilitate their entry into cells for intracellular detection. The non-ionic structure also precludes undesired electrostatic reactions with ionic sites on biological components and structures.

Abstract: Novel molecular transporter compositions and their use for transporting bioactive substances into cells in living animals are disclosed. To afford in vivo delivery, the composition is covalently linked to the bioactive substance and the resultant composite structure is introduced into the subject. The transporter composition includes multiple guanidine moieties on a dendrimeric scaffold having a tri-functional core. The tri-functional core is a phosphorodiamidate or phosphoramide moiety.

Abstract: Morpholinos are widely used to block the activity of selected single-stranded genetic sequences. This invention comprises Morpholinos containing one or more integral photolinkers (Photo-Morpholinos) wherein the photolinkers are directly incorporated into the sequence of a Morpholino, where the photolinker has a size and structure which emulates the size and structure of a Morpholino subunit. This integrated photolinker design substantially simplifies and reduces cost of production relative to earlier photocleavable compositions. The invention also comprises use of these Photo-Morpholinos for modulating the expression of any selected gene transcript at any selected time and at any selected site simply by exposure to light. These Photo-Morpholinos afford a new use wherein a gene transcript is rendered inactive by contacting with a Photo-Morpholino—and then later exposure to light cleaves the Photo-Morpholino to inactive fragments—thereby reactivating that previously inactivated gene transcript.

Abstract: Preparations of novel molecular transporter compositions and their use for transporting bioactive substances into cells in living animals are disclosed. To afford in vivo delivery, the composition is covalently linked to the bioactive substance and the resultant composite structure is introduced into the subject. The transporter composition includes multiple guanidine moieties on a dendrimeric scaffold having a triazine core.

Abstract: Embedder compositions effective for detecting or killing cells in acidic areas of tumors are described. Each composition includes an embedder peptide which at pH 7.2 and above is poly-anionic and so repels from cells in normal tissues, but at lower pH in hypoxic areas of tumors the embedder peptide converts to a non-ionic lipophilic form effective to embed into membranes of cells. Each composition also includes a cargo component which cannot be pulled across cell membranes by the embedder peptide and which is effective for detecting or killing cells in whose membranes the embedder peptide has embedded.

Abstract: Improved transporter compositions effective for detecting or killing cells in acidic areas of tumors are described. Each composition includes a transporter peptide which at pH 7.2 and above is poly-anionic and so repels from cells in normal tissues, but at lower pH in hypoxic areas of tumors the transporter peptide converts to a non-ionic lipophilic form which transports across membranes of cells. Each composition also includes a cargo component which can be pulled across cell membranes by the transporter peptide and which is effective for detecting or killing cells into which the transporter composition has entered.

Abstract: Weak-base amphiphilic delivery peptide compositions are described for use in delivering large polar substances (cargo) into the cytosol of animal cells via an indirect endocytosis-mediated delivery process. The delivery peptides, which are predominantly non-ionic at neutral pH, bind but do not permeabilize cell membranes. After endocytosis of both delivery peptides and cargo, acidification of the endosome converts the delivery peptides to their polycationic form, whereupon they permeabilize the endosomal membrane and allow co-endocytosed cargo to pass from the endosome to the cytosol of the cell.

Abstract: The invention relates to a composition, solution, and method for delivering desired substances into the cytosol of living eucaryotic cells. The composition includes a poly(ethylene glycol) component having a designated molecular weight in the range between about 300 and about 900 daltons, and a carbohydrate component which is membrane impermeable and water soluble. The osmotic delivery solution delivers reporter-tagged molecules and complexes, drugs, antisense and antigene oligos, RNAs, DNAs, peptides, proteins, carbohydrates, and the like into cultured cells using an improved osmotic delivery method. The method may also be used for extracorporal therapy. In a particularly preferred embodiment of extracorporal therapy, the desired substance delivered into the cytosol of the cells is a Morpholino antisense oligo.