M Ángeles Muñoz-Fernández *

Autor invitado por SIIC

El uso del dendrímero carbosilano 2G-NN16 como transfectante de ARNsi anti-VIH, en células del SNC, constituye una estrategia novedosa para el tratamiento antiviral en reservorios anatómicos del VIH.

LOS DENDRÍMEROS CARBOSILANO SON CAPACES DE TRANSFECTAR ASTROCITOS HUMANOS CON ARNSI CONTRA EL VIRUS DE LA INMUNODEFICIENCIA HUMANA (VIH)

Las manifestaciones neurológicas de la infección por el VIH son refractarias al tratamiento antirretroviral actual (TARGA). En este trabajo se propone el uso del dendrímero carbosilano 2G-NN16 como transfectante de siRNA anti-VIH en células del SNC y como tratamiento para la infección de astrocitos por aislados X4-VIH y R5-VIH.

*M Ángeles Muñoz-Fernández
describe para SIIC los aspectos relevantes de su trabajo
CARBOSILANE DENDRIMERS TO TRANSFECT HUMAN ASTROCYTES WITH SMALL INTERFERING RNA TARGETING HUMAN IMMUNODEFICIENCY VIRUS
Institución principal de la investigación
*Hospital General Universitario Gregorio Marañón, Madrid, España
Imprimir nota

Comprar este artículo
Otros artículos escogidos

Referencias bibliográficas
Sacktor N, Lyles RH, Skolasky R, et al. HIV-associated neurologic disease incidence changes: multicenter AIDS cohort study, 1990-1998. Neurology 56(2):257-260, 2001. Lindl KA, Marks DR, Kolson DL, et al. HIV-associated neurocognitive disorder: pathogenesis and therapeutic opportunities. J Neuroimmune Pharmacol.
Ellis RJ, Deutsch R, Heaton RK, et al. Neurocognitive impairment is an independent risk factor for death in HIV infection. San Diego HIV Neurobehavioral Research Center Group. Arch Neurol 54(4):416-424, 1997.
Sanchez-Ramon S, Resino S, Bellon Cano JM, et al. Neuroprotective effects of early antiretrovirals in vertical HIV infection. Pediatr Neurol 29(3):218-221, 2003.
Canto-Nogues C, Sanchez-Ramon S, Alvarez S, et al. HIV-1 infection of neurons might account for progressive HIV-1-associated encephalopathy in children. J Mol Neurosci 27(1):79-89, 2005.
Gonzalez-Scarano F, Martin-Garcia J. The neuropathogenesis of AIDS. Nat Rev Immunol 5(1):69-81, 2005.
Kerza-Kwiatecki AP, Amini S. CNS as an HIV-1 reservoir: BBB and drug delivery. J Neurovirol 5(2):113-114, 1999.
Brew BJ. HIV, the brain, children, HAART and 'neuro-HAART': a complex mix. Aids 23(14):1909-1910, 2009.
Ghafouri M, Amini S, Khalili K, et al. HIV-1 associated dementia: symptoms and causes. Retrovirology 3:28, 2006.
McArthur JC, Haughey N, Gartner S, et al. Human immunodeficiency virus-associated dementia: an evolving disease. J Neurovirol 9(2):205-221, 2003.
Clifford DB. HIV-associated neurocognitive disease continues in the antiretroviral era. Top HIV Med 16(2):94-98, 2008.
Tozzi V, Balestra P, Bellagamba R, et al. Persistence of neuropsychologic deficits despite long-term highly active antiretroviral therapy in patients with HIV-related neurocognitive impairment: prevalence and risk factors. J Acquir Immune Defic Syndr 45(2):174-182, 2007.
Wynn HE, Brundage RC, Fletcher CV. Clinical implications of CNS penetration of antiretroviral drugs. CNS Drugs 16(9):595-609, 2002.
Sharp PA. RNA interference: 2001. Genes Dev 15(5):485-490, 2001.
Coburn GA, Cullen BR. siRNAs: a new wave of RNA-based therapeutics. J Antimicrob Chemother 51(4):753-756, 2003.
Lee MT, Coburn GA, McClure MO, et al. Inhibition of human immunodeficiency virus type 1 replication in primary macrophages by using Tat- or CCR5-specific small interfering RNAs expressed from a lentivirus vector. J Virol 77(22):11964-11972, 2003. Han W, Wind-Rotolo M, Kirkman RL, et al. Inhibition of human immunodeficiency virus type 1 replication by siRNA targeted to the highly conserved primer binding site. Virology 330(1):221-232, 2004.
Novina CD, Murray MF, Dykxhoorn DM, et al. siRNA-directed inhibition of HIV-1 infection. Nat Med 7:681-686, 2002.
Nishitsuji H, Kohara M, Kannagi M, et al. Effective suppression of human immunodeficiency virus type 1 through a combination of short- or long-hairpin RNAs targeting essential sequences for retroviral integration. J Virol 80(15):7658-7666, 2006. Pomerantz RJ. RNA interference meets HIV-1: will silence be golden? Nat Med 8(7):659-660, 2002.
Liu YP, Haasnoot J, ter Brake O, et al. Inhibition of HIV-1 by multiple siRNAs expressed from a single microRNA polycistron. Nucleic Acids Res 36(9):2811-2824, 2008.
Kumar P, Ban HS, Kim SS, et al. T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice. Cell 134(4):577-586, 2008.
Song E, Zhu P, Lee SK, et al. Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors. Nat Biotechnol 23(6):709-717, 2005.
Mintzer MA, Simanek EE. Nonviral vectors for gene delivery. Chem Rev 109(2):259-302, 2009.
Whitehead KA, Langer R, Anderson DG. Knocking down barriers: advances in siRNA delivery. Nat Rev Drug Discov 8(2):129-138, 2009.
Fischer D, Li Y, Ahlemeyer B, et al. In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis. Biomaterials 24(7):1121-1131, 2003.
Kurreck J. RNA interference: from basic research to therapeutic applications. Angew Chem Int Ed Engl 48(8):1378-1398, 2009.
Ortega P, Bermejo JF, Chonco L, et al. Novel water-soluble carbosilane dendrimers: synthesis and biocompatibility. Eur J Inorg Chem 7:1388-1396, 2006.
Weber N, Ortega P, Clemente MI, et al. Characterization of carbosilane dendrimers as effective carriers of siRNA to HIV-infected lymphocytes. J Control Release 132(1):55-64, 2008.
Fréchet JMJ. Dendrimers and other dendritic macromolecules: from building blocks to functional assemblies in nanoscience and nanotechnology. J Polymer Sci Part A: Polymer Chem 1758(3):290-300, 2003.
Loscher W, Potschka H. Role of drug efflux transporters in the brain for drug disposition and treatment of brain diseases. Prog Neurobiol 76(1):22-76, 2005.
Bermejo JF, Ortega P, Chonco L, et al. Water-soluble carbosilane dendrimers: synthesis biocompatibility and complexation with oligonucleotides; evaluation for medical applications. Chemistry 13(2):483-495, 2007.
Chonco L, Bermejo-Martin JF, Ortega P, et al. Water-soluble carbosilane dendrimers protect phosphorothioate oligonucleotides from binding to serum proteins. Org Biomol Chem 5(12):1886-1893, 2007.
Song E, Lee SK, Dykxhoorn DM, et al. Sustained small interfering RNA-mediated human immunodeficiency virus type 1 inhibition in primary macrophages. J Virol 77(13):7174-7181, 2003.
Capodici J, Kariko K, Weissman D. Inhibition of HIV-1 infection by small interfering RNA-mediated RNA interference. J Immunol 169(9):5196-5201, 2002.
Das AT, Brummelkamp TR, Westerhout EM, et al. Human immunodeficiency virus type 1 escapes from RNA interference-mediated inhibition. J Virol 78(5):26, 2004. Toborek M, Lee YW, Flora G, et al. Mechanisms of the blood-brain barrier disruption in HIV-1 infection. Cell Mol Neurobiol 25(1):181-199, 2005.
Kuo YC, Chen HH. Effect of nanoparticulate polybutylcyanoacrylate and methylmethacrylate-sulfopropylmethacrylate on the permeability of zidovudine and lamivudine across the in vitro blood-brain barrier. Int J Pharm 327(1-2):160-169, 2006. Hartig PC, Hunter 3rd ES. Gene delivery to the neurulating embryo during culture. Teratology 58(3-4):103-112, 1998.
Sata M, Walsh K. Endothelial cell apoptosis induced by oxidized LDL is associated with the down-regulation of the cellular caspase inhibitor FLIP. J Biol Chem 273(50):33103-33106, 19988.
Kolchinsky P, Kiprilov E, Sodroski J. Increased neutralization sensitivity of CD4-independent human immunodeficiency virus variants. J Virol 75(5):2041-2050, 2001. Trillo-Pazos G, Diamanturos A, Rislove L, et al.Detection of HIV-1 DNA in microglia/macrophages, astrocytes and neurons isolated from brain tissue with HIV-1 encephalitis by laser capture microdissection. Brain Pathol 13(2):144-154, 2003. Alvarez Losada S, Canto-Nogues C, Munoz-Fernandez MA. A new possible mechanism of human immunodeficiency virus type 1 infection of neural cells. Neurobiol Dis 11(3):469-478, 2002.
Liu Y, Liu H, Kim BO, et al.CD4-independent infection of astrocytes by human immunodeficiency virus type 1: requirement for the human mannose receptor. J Virol 78(8):4120-4133, 2004.
Jevprasesphant R, Penny J, Jalal R, et al. The influence of surface modification on the cytotoxicity of PAMAM dendrimers. Int J Pharm 252(1-2):263-266, 2003.
Vogelbaum MA, Tong JX, Higashikubo R, et al. Transfection of C6 glioma cells with the bax gene and increased sensitivity to treatment with cytosine arabinoside. J Neurosurg 88(1):99-105, 1999.
Lampela P, Soininen P, Urtti A, et al. Synergism in gene delivery by small PEIs and three different nonviral vectors. Int J Pharm 270(1-2):175-184, 2004.
Alvarez S, Jimenez JL, Serramia MJ, et al. Lack of association of HIV-1 biological or molecular properties with neurotropism for brain cells. J Mol Neurosci 29(2):131-144, 2006.
Gorry PR, Bristol G, Zack JA, et al. Macrophage tropism of human immunodeficiency virus type 1 isolates from brain and lymphoid tissues predicts neurotropism independent of coreceptor specificity. J Virol 75(21):10073-10089, 2001.
MacKay JA, Deen DF, Szoka Jr FC. Distribution in brain of liposomes after convection enhanced delivery: modulation by particle charge, particle diameter, and presence of steric coating. Brain Res 1035(2):139-153, 2005.
Lockman PR, Koziara JM, Mumper RJ, et al. Nanoparticle surface charges alter blood-brain barrier integrity and permeability. J Drug Target 12(9-10):635-641, 2004.
Fenart L, Casanova A, Dehouck B, et al. Evaluation of effect of charge and lipid coating on ability of 60-nm nanoparticles to cross an in vitro model of the blood-brain barrier. J Pharmacol Exp Ther 291(3):1017-1022, 1999.
Huang RQ, Qu YH, Ke WL, et al. Efficient gene delivery targeted to the brain using a transferrin-conjugated polyethyleneglycol-modified polyamidoamine dendrimer. Faseb J 21(4):1117-1125, 2007.
Dehouck B, Fenart L, Dehouck MP, et al. A new function for the LDL receptor: transcytosis of LDL across the blood-brain barrier. J Cell Biol 138(4):877-889, 1997.
Balazs Z, Panzenboeck U, Hammer A, et al. Uptake and transport of high-density lipoprotein (HDL) and HDL-associated alpha-tocopherol by an in vitro blood-brain barrier model. J Neurochem 89(4):939-950, 2004.
Yousif S, Marie-Claire C, Roux F, et al. Expression of drug transporters at the blood-brain barrier using an optimized isolated rat brain microvessel strategy. Brain Res 1134(1):1-11, 2007.
Giovannoni G, Miller RF, Heales SJ, et al. Elevated cerebrospinal fluid and serum nitrate and nitrite levels in patients with central nervous system complications of HIV-1 infection: a correlation with blood-brain-barrier dysfunction. J Neurol Sci 156(1):53-58, 1998.
Petito CK, Cash KS. Blood-brain barrier abnormalities in the acquired immunodeficiency syndrome: immunohistochemical localization of serum proteins in postmortem brain. Ann Neurol 32(5):658-666, 1992.

Otros artículos de M Ángeles Muñoz-Fernández

Gonzalo T, Clemente MI, Chonco L, Weber ND, Díaz L, Serramía MJ, Gras R, Ortega P, de la Mata FJ, Gómez R, Lopez-Fernández LA, Muñoz-Fernández MA, Jiménez JL. Gene therapy in HIV-infected cells to decrease viral impact by using an alternative delivery method. ChemMedChem 5(6):921-929, 2010.
Posadas I, López-Hernández B, Clemente MI, Jiménez JL, Ortega P, de la Mata J, Gómez R, Muñoz-Fernández MA, Ceña V. Highly efficient transfection of rat cortical neurons using carbosilane dendrimers unveils a neuroprotective role for HIF-1alpha in early chemical hypoxia-mediated neurotoxicity. Pharm Res 26(5):1181-1191, 2009.
Pedziwiatr E, Shcharbin D, Chonco L, Ortega P, de la Mata FJ, Gómez R, Klajnert B, Bryszewska M, Muñoz-Fernandez MA. Binding properties of water-soluble carbosilane dendrimers. J Fluoresc 19(2):267-275, 2009. Epub 2008 Aug 3
Weber N, Ortega P, Clemente MI, Shcharbin D, Bryszewska M, de la Mata FJ, Gómez R, Muñoz-Fernández MA. Characterization of carbosilane dendrimers as effective carriers of siRNA to HIV-infected lymphocytes.J Control Release 132(1):55-64, 2008. Epub 2008 Aug 5.
Blanco A, Alvarez S, Fresno M, Muñoz-Fernández MA. Extracellular HIV-Tat induces cyclooxygenase-2 in glial cells through activation of nuclear factor of activated T cells. J Immunol 180(1):530-540, 2008.
Alvarez S, Serramía MJ, Fresno M, Muñoz-Fernández MA. HIV-1 envelope glycoprotein 120 induces cyclooxygenase-2 expression in astrocytoma cells through a nuclear factor-kappaB-dependent mechanism. Neuromolecular Med 9(2):179-193, 2009.
Shcharbin D, Pedziwiatr E, Chonco L, Bermejo-Martín JF, Ortega P, de la Mata FJ, Eritja R, Gómez R, Klajnert B, Bryszewska M, Muñoz-Fernandez MA. Analysis of interaction between dendriplexes and bovine serum albumin. Biomacromolecules 8(7):2059-2062, 2007. Epub 2007 Jun 21.
Chonco L, Bermejo-Martín JF, Ortega P, Shcharbin D, Pedziwiatr E, Klajnert B, de la Mata FJ, Eritja R, Gómez R, Bryszewska M, Muñoz-Fernandez MA. Water-soluble carbosilane dendrimers protect phosphorothioate oligonucleotides from binding to serum proteins. Org Biomol Chem 5(12):1886-1893, 2007. Epub 2007 May 14.
Alvarez S, Jiménez JL, Serramía MJ, González M, Cantó-Nogués C, Muñoz-Fernández MA. Lack of association of HIV-1 biological or molecular properties with neurotropism for brain cells. J Mol Neurosci 29(2):131-134, 2006.

Para comunicarse con M Ángeles Muñoz-Fernández mencionar a SIIC como referencia:
mmunoz.hgugm@salud.madrid.org

---

Acerca del trabajo completo

LOS DENDRÍMEROS CARBOSILANO SON CAPACES DE TRANSFECTAR ASTROCITOS HUMANOS CON ARNSI CONTRA EL VIRUS DE LA INMUNODEFICIENCIA HUMANA (VIH)

Título original en castellano
LOS DENDRIMEROS CARBOSILANO SON CAPACES DE TRANSFECTAR ASTROCITOS HUMANOS CON SIRNAS CONTRA EL VIRUS DE LA INMUNODEFICIENCIA HUMANA (VIH).

Autores
M Ángeles Muñoz-Fernández¹, Jose Luis Jiménez Fuentes², María Isabel Clemente Mayoral³, Jose Luis Jiménez Fuentes⁴, María Isabel Clemente Mayoral⁵
1 Doctora en Biologia, Investiga, Laboratorio de Inmunobiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, España, Adjunta del Servicio de Inmunología.
2 Dr en Biología. Investigador, Plataforma de Laboratorio, Hospital General Universitario Gregorio Marañón, C/doctor Esquerdo 46, Madrid, Spain. Ciber de Bioingeniería, Biomateriales y Nanomedicina (ciber-bbn), Instituto de Salud Carlos Iii, Spain., Dr en Biología. Investigador
3 Biologa. Investigación, Ciber de Bioingeniería, Biomateriales y Nanomedicina (ciber-bbn), Instituto de Salud Carlos Iii, Spain. Laboratorio de Inmunobiología Molecular, Hospital General Universitario Gregorio Marañón, C/doctor Esquerdo 46,
4 Dr en Biología. Investigador, Plataforma de Laboratorio, Hospital General Universitario Gregorio Marañón, C/doctor Esquerdo 46, Madrid, Spain. Ciber de Bioingeniería, Biomateriales y Nanomedicina (ciber-bbn), Instituto de Salud Carlos Iii, Spain., Dr en Biología. Investigador
5 Biologa. Investigación, Ciber de Bioingeniería, Biomateriales y Nanomedicina (ciber-bbn), Instituto de Salud Carlos Iii, Spain. Laboratorio de Inmunobiología Molecular, Hospital General Universitario Gregorio Marañón, C/doctor Esquerdo 46,

Acceso a la fuente original
Biodrugs
http://link.springer.com/journal/40259

El artículo se relaciona estrictamente con las especialidades de siicsalud
El artículo se conecta secundariamente con las especialidades