Dendrimer Delivery of Oligonucleotides

AbstractFactors limiting the pharmacological effectiveness of antisense oligonucleotides include serum stability and the fact that these agents are inefficiently transported to their sites of action in the cytoplasm and nucleus. Polyamidoamine (PAMAM) dendrimers are nonlinear polycationic cascade polymers composed of interconnected ethylenediamine molecules that are able to bind oligonucleotides electrostatically. This new complex potentially reduces metabolic degradation of phosphodiester oligonucleotides in the serum and in the lysosome. Dendrimers also have the potential to increase oligonucleotide cellular uptake, thus augmenting their pharmacological effectiveness. We studied various dendrimer generations and their ability to interact with phosphodiester oligonucleotides. Alterations in pH and in ionic strength were studied for their effects on the dendrimer–oligonucleotide complex. A fluorescent-labeled oligonucleotide was utilized to study these interactions through a fluorescence anisotropy method...

[1]  A. Urtti,et al.  Oligonucleotide-cationic liposome interactions. A physicochemical study. , 1994, Biochimica et biophysica acta.

[2]  P. Singh,et al.  Starburst dendrimers: enhanced performance and flexibility for immunoassays. , 1994, Clinical chemistry.

[3]  J. Ojwang,et al.  Inhibition of Friend murine leukemia virus activity by guanosine/thymidine oligonucleotides. , 1994, Antiviral research.

[4]  K. Altmann,et al.  The effects of 2′- and 3′-alkyl substituents on oligonucleotide hybridization and stability , 1994 .

[5]  K. Merchant.  c-fos Antisense Oligonucleotide Specifically Attenuates Haloperidol-Induced Increases in Neurotensin/neuromedin N mRNA Expression in Rat Dorsal Striatum , 1994, Molecular and Cellular Neuroscience.

[6]  K. Mechtler,et al.  Carbohydrate receptor-mediated gene transfer to human T leukaemic cells. , 1994, Glycobiology.

[7]  Charles L. Wilkins,et al.  Phenylacetylene Dendrimers by the Divergent, Convergent, and Double-Stage Convergent Methods , 1994 .

[8]  B. Froehler,et al.  Development of Antisense Therapeutics: Implications for Cancer Gene Therapy , 1994, Annals of the New York Academy of Sciences.

[9]  R. Barth,et al.  Boron neutron capture therapy of primary and metastatic brain tumors , 1994, Molecular and chemical neuropathology.

[10]  P C Lauterbur,et al.  Dendrimer‐based metal chelates: A new class of magnetic resonance imaging contrast agents , 1994, Magnetic resonance in medicine.

[11]  T. Coleman,et al.  Antisense inhibition of the p65 subunit of NF-kappa B blocks tumorigenicity and causes tumor regression. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[12]  F. Szoka,et al.  Polyamidoamine cascade polymers mediate efficient transfection of cells in culture. , 1993, Bioconjugate chemistry.

[13]  C. Franceschi,et al.  Inhibition of c-fes expression by an antisense oligomer causes apoptosis of HL60 cells induced to granulocytic differentiation , 1993, The Journal of experimental medicine.

[14]  J. Pow-Sang,et al.  Antisense DNA inhibition of tumor growth induced by c-Ha-ras oncogene in nude mice. , 1993, Cancer research.

[15]  B. Chiasson,et al.  Antisense oligonucleotide eliminates in vivo expression of c-fos in mammalian brain. , 1992, European journal of pharmacology.

[16]  S. Dey,et al.  Antisense c-myc effects on preimplantation mouse embryo development. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[17]  R. Juliano,et al.  Liposome delivery of antisense oligonucleotides: adsorption and efflux characteristics of phosphorothioate oligodeoxynucleotides , 1992 .

[18]  K Zatloukal,et al.  Coupling of adenovirus to transferrin-polylysine/DNA complexes greatly enhances receptor-mediated gene delivery and expression of transfected genes. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[19]  M. Hayashi,et al.  Inhibition of mouse hepatitis virus multiplication by an oligonucleotide complementary to the leader RNA. , 1992, The Journal of veterinary medical science.

[20]  C. Bennett,et al.  Cationic lipids enhance cellular uptake and activity of phosphorothioate antisense oligonucleotides. , 1992, Molecular pharmacology.

[21]  P. Herman,et al.  c-myc antisense oligonucleotides inhibit the colony-forming capacity of Colo 320 colonic carcinoma cells. , 1992, The Journal of clinical investigation.

[22]  N. Thuong,et al.  Synthesis and physicochemical properties of oligonucleotides built with either α-L or β-L nucleotides units and covalently linked to an acridine derivative , 1991 .

[23]  A. Murakami,et al.  Fluorescent-labeled oligonucleotide probes: detection of hybrid formation in solution by fluorescence polarization spectroscopy. , 1991, Nucleic acids research.

[24]  William A. Goddard,et al.  Starburst Dendrimers: Molecular‐Level Control of Size, Shape, Surface Chemistry, Topology, and Flexibility from Atoms to Macroscopic Matter , 1990 .

[25]  R. Barth,et al.  Boronated starburst dendrimer-monoclonal antibody immunoconjugates: evaluation as a potential delivery system for neutron capture therapy. , 1994, Bioconjugate chemistry.

[26]  J. Hughes,et al.  Influence of base composition on membrane binding and cellular uptake of 10-mer phosphorothioate oligonucleotides in Chinese hamster ovary (CHRC5) cells. , 1994, Antisense research and development.

[27]  D. Praseuth,et al.  Unexpected effect of an anti-human immunodeficiency virus intermolecular triplex-forming oligonucleotide in an in vitro transcription system due to RNase H-induced cleavage of the RNA transcript. , 1993, Antisense research and development.

[28]  B. Lebleu,et al.  Poly(L-lysine)-conjugated oligonucleotides promote sequence-specific inhibition of acute HIV-1 infection. , 1992, Antisense research and development.

[29]  R. Kole,et al.  Stability of antisense DNA oligodeoxynucleotide analogs in cellular extracts and sera. , 1991, Life sciences.