Abstract: A low toxicity, highly efficient transfection composition is described with an amphipathic compound containing at least one imidazole. The composition may be used in the process of transfecting nucleic acids into an animal cell.

Abstract: The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to hepatocytes in vivo. Targeted RNAi polynucleotides are administered together with co-targeted melittin delivery peptides. Delivery peptides provide membrane penetration function for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness to the delivery peptides.

Abstract: The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to hepatocytes in vivo. Targeted RNAi polynucleotides are administered together with co-targeted melittin delivery peptides. Delivery peptides provide membrane penetration function for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness to the delivery peptides.

Abstract: The present invention is directed compositions for delivery of RNA interference (RNAi) polynucleotides to cells in vivo. The compositions comprise amphipathic membrane active polyamines reversibly modified with enzyme cleavable dipeptide-amidobenzyl-carbonate masking agents. Modification masks membrane activity of the polymer while reversibility provides physiological responsiveness. The reversibly modified polyamines (dynamic polyconjugate or DPC) are further covalently linked to an RNAi polynucleotide or co-administered with a targeted RNAi polynucleotide-targeting molecule conjugate.

Abstract: A process is described for the delivery of a therapeutic polynucleotide to limb muscle tissue suffering from or potentially suffering from Muscular Dystrophy. The polynucleotide is inserted into a mammalian limb vessel such as an artery. Delivery efficiency and distribution is enhanced by combining injection of a solution containing the polynucleotide with the use of an externally applied cuff.

Abstract: Chelator containing compounds are utilized in the delivery of molecules and polymers to animal cells. At least one chelator such as crown ether is attached to a polymer and then associated with another polymer. An ion is then added to the mixture thereby forming condensed polymer. In condensed form and in complex with the chelator, polymer can be delivered to a cell.

Abstract: A method for delivering a naked or isolated polynucleotide to the interior of a cell in a vertebrate, comprising the interstitial introduction of a naked polynucleotide into a tissue of the vertebrate where the polynucleotide is taken up by the cells of the tissue and exerts a therapeutic effect on the vertebrate. The method can be used to deliver a therapeutic polypeptide to the cells of the vertebrate, to provide an immune response upon in vivo translation of the polynucleotide, to deliver antisense polynucleotides, to deliver receptors to the cells of the vertebrate, or to provide transitory gene therapy.

Abstract: A labile disulfide-containing compound under physiological conditions containing a labile disulfide bond and a transduction signal.

Abstract: Disclosed is expression of zeta negative and zeta positive nucleic acids or nucleic acid complexes using a dystrophin gene in a process for providing nucleic acid expression in a striated (skeletal or cardiac) muscle cell for the purpose of providing a change to the endogenous properties of the cell for cells affected by muscular dystrophy.

Abstract: Described is a process for intravascular delivery of a polynucleotide to an extravascular cell of a mammal to inhibit gene expression. A polynucleotide containing sequence that is similar to a sequence in the gene to be expressed is made and inserted into a vessel in the mammal. The polynucleotide is delivered to a cell wherein expression of the gene is inhibited.

Abstract: Processes are described for obtaining high levels of gene expression in primates after injection of nucleic acid to the liver via the lumen of the hepatic vein. The described process results in high level of gene expression with transient increases in liver enzymes.

Abstract: An polyampholyte is utilized in a condensed polynucleotide complex for purposes of nucleic acid delivery to a cell. The complex can be formed with an appropriate amount of positive and/or negative charge such that the resulting complex can be delivered to the extravascular space and may be further delivered to a cell.

Abstract: We describe pH-sensitive endosomolytic polymers, delivery particles containing pH-sensitive endosomolytic polymers. The described particles are capable of delivering polynucleotides to cells from the peripheral circulation with subsequent release from endosomes. The endosomolytic polymers are inactive outside the cell but disrupt membranes upon exposure to an acidified endosomal compartment.

Abstract: The present invention relates to methods for delivering a genetic immunogen, comprising a nucleic acid capable of expressing an antigen, optionally complexed with a polymer. The nucleic acid is delivered to the host via hydrodynamic intravascular injection resulting in expression of an encoded antigen in extravascular cells and induction of an antigen-specific immune response.

Abstract: Methods are described for modifying nucleic acids to facilitate delivery of the nucleic acids to cells. Compounds which interact with of modify nucleic acids are interacted with the nucleic acids within reverse micelles.

Abstract: Processes are described for obtaining high levels of gene expression in primates after injection of nucleic acid to the liver via the lumen of the hepatic vein. The described process results in high level of gene expression with transient increases in liver enzymes.

Abstract: Compounds and methods are provided for a single-pot covalent attachment of a label to nucleic acids comprising forming a covalently attachable labeling reagent for alkylating the molecule. Then, combining the covalently attachable labeling reagent with a mixture containing the molecule, under conditions wherein the labeling reagent has reactivity with the molecule thereby forming a covalent bond.

Abstract: Compounds and methods are provided for a single-pot covalent attachment of a label to an siRNA comprising forming a covalently attachable labeling reagent for alkylating the molecule. Then, combining the covalently attachable labeling reagent with a mixture containing the molecule, under conditions wherein the labeling reagent has reactivity with the molecule thereby forming a covalent bond.

Abstract: A method of forming polymers in the presence of nucleic acid using template polymerization. These methods can be used for the delivery of nucleic acids, for condensing the nucleic acid, for forming nucleic acid binding polymers, for forming supramolecular complexes containing nucleic acid and polymer, and for forming an interpolyelectrolyte complex.

Abstract: We describe compounds that bind to and are internalized by hepatocytes. Association of these compounds to other molecules or complexes can be used to target the molecules or complexes to hepatocytes in vivo or in vitro.