Small Interfering RNAs and their Delivery Systems: A Novel Powerful Tool for the Potential Treatment of HIV Infections

Author(s): Azam Bolhassani*, Alireza Milani

Journal Name: Current Molecular Pharmacology

Volume 13 , Issue 3 , 2020

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Abstract:

Small interfering RNAs (siRNAs) have rapidly developed into biomedical research as a novel tool for the potential treatment of various human diseases. They are based on altered gene expression. In spite of the availability of highly active antiretroviral therapy (HAART), there is a specific interest in developing siRNAs as a therapeutic agent for human immunodeficiency virus (HIV) due to several problems including toxicity and drug resistance along with long term treatment. The successful use of siRNAs for therapeutic goals needs safe and effective delivery to specific cells and tissues. Indeed, the efficiency of gene silencing depends on the potency of the carrier used for siRNA delivery. The combination of siRNA and nano-carriers is a potent method to prevent the limitations of siRNA formulation. Three steps were involved in non-viral siRNA carriers such as the complex formation of siRNA with a cationic carrier, conjugation of siRNA with small molecules, and encapsulation of siRNA within nanoparticles.

In this mini-review, the designed siRNAs and their carriers are described against HIV-1 infections both in vitro and in vivo.

Keywords: HIV infection, siRNA, delivery system, in vitro and in vivo studies, cancer, RNAs.

[1]
Wheeler, L.A. Silencing sexually transmitted infections: topical siRNA-based interventions for the prevention of HIV and HSV. Infect. Dis. Obstet. Gynecol., 2014, 2014125087
[http://dx.doi.org/10.1155/2014/125087] [PMID: 24526828]
[2]
Kadkhodayan, S.; Jafarzade, B.S.; Sadat, S.M.; Motevalli, F.; Agi, E.; Bolhassani, A. Combination of cell penetrating peptides and heterologous DNA prime/protein boost strategy enhances immune responses against HIV-1 Nef antigen in BALB/c mouse model. Immunol. Lett., 2017, 188, 38-45.
[http://dx.doi.org/10.1016/j.imlet.2017.06.003] [PMID: 28602843]
[3]
Sarisozen, C.; Salzano, G.; Torchilin, V.P. Recent advances in siRNA delivery. Biomol. Concepts, 2015, 6(5-6), 321-341.
[http://dx.doi.org/10.1515/bmc-2015-0019] [PMID: 26609865]
[4]
Bennasser, Y.; Le, S.Y.; Benkirane, M.; Jeang, K.T. Evidence that HIV-1 encodes an siRNA and a suppressor of RNA silencing. Immunity, 2005, 22(5), 607-619.
[http://dx.doi.org/10.1016/j.immuni.2005.03.010] [PMID: 15894278]
[5]
Tuzmen, S.; Yalinca, Z. Attractive approaches in siRNA delivery using polymer bio-based carrier systems. Anadolu Uni. J. Sci. Technol. C- Life Sci. Biotechnol., 2018, 7(1), 74-89.
[6]
Mishra, V.; Kesharwani, P.; Jain, N.K. siRNA nanotherapeutics: a Trojan horse approach against HIV. Drug Discov. Today, 2014, 19(12), 1913-1920.
[http://dx.doi.org/10.1016/j.drudis.2014.09.019] [PMID: 25281591]
[7]
Tyagi, A.; Ahmed, F.; Thakur, N.; Sharma, A.; Raghava, G.P.S.; Kumar, M. HIVsirDB: a database of HIV inhibiting siRNAs. PLoS One, 2011, 6(10)e25917
[http://dx.doi.org/10.1371/journal.pone.0025917] [PMID: 22022467]
[8]
Vlachakis, D.; Tsiliki, G.; Pavlopoulou, A.; Roubelakis, M.G.; Tsaniras, S.C.; Kossida, S. Antiviral stratagems against HIV-1 using RNA interference (RNAi) technology. Evol. Bioinform. Online, 2013, 9, 203-213.
[http://dx.doi.org/10.4137/EBO.S11412] [PMID: 23761954]
[9]
Rossi, J.J. RNAi as a treatment for HIV-1 infection. Biotechniques,, 2006, 40((Suppl.4-5)), 25-29.
[http://dx.doi.org/10.2144/000112167] [PMID: 16629384]
[10]
Kim, S.S.; Peer, D.; Kumar, P.; Subramanya, S.; Wu, H.; Asthana, D.; Habiro, K.; Yang, Y.G.; Manjunath, N.; Shimaoka, M.; Shankar, P. RNAi-mediated CCR5 silencing by LFA-1-targeted nanoparticles prevents HIV infection in BLT mice. Mol. Ther., 2010, 18(2), 370-376.
[http://dx.doi.org/10.1038/mt.2009.271] [PMID: 19997090]
[11]
Kim, S.S.; Subramanya, S.; Peer, D.; Shimaoka, M.; Shankar, P. Antibody-mediated delivery of siRNAs for anti-HIV therapy. Methods in molecular biology. Book series,, 2011, 721,, 339-353.
[http://dx.doi.org/10.1007/978-1-61779-037-9_21]
[12]
Adesina, S.K.; Akala, E.O. Nanotechnology approaches for the delivery of exogenous siRNA for HIV therapy. Mol. Pharm., 2015, 12(12), 4175-4187.
[http://dx.doi.org/10.1021/acs.molpharmaceut.5b00335] [PMID: 26524196]
[13]
Milani, A.; Bolhassani, A.; Shahbazi, S.; Motevalli, F.; Sadat, S.M.; Soleymani, S. Small heat shock protein 27: An effective adjuvant for enhancement of HIV-1 Nef antigen-specific immunity. Immunol. Lett., 2017, 191, 16-22.
[http://dx.doi.org/10.1016/j.imlet.2017.09.005] [PMID: 28917624]
[14]
Bolhassani, A.; Kardani, K.; Vahabpour, R.; Habibzadeh, N.; Aghasadeghi, M.R.; Sadat, S.M.; Agi, E. Prime/boost immunization with HIV-1 MPER-V3 fusion construct enhances humoral and cellular immune responses. Immunol. Lett., 2015, 168(2), 366-373.
[http://dx.doi.org/10.1016/j.imlet.2015.10.012] [PMID: 26518142]
[15]
Khairkhah, N.; Namvar, A.; Kardani, K.; Bolhassani, A. Prediction of cross-clade HIV-1 T-cell epitopes using immunoinformatics analysis. Proteins, 2018, 86(12), 1284-1293.
[http://dx.doi.org/10.1002/prot.25609] [PMID: 30260061]
[16]
Pomerantz, R.J. RNA interference meets HIV-1: will silence be golden? Nature Medicine,, 2002, 8, 659-660.
[17]
Novina,, C.D.,; Murray,, M.F.,; Dykxhoorn,, D.M.,; Beresford, P.J.; Riess, J.; Lee, S.K.; Collman, R.G.; Waterhouse, P.M.; Wang, M.B.; Lough, T. Gene silencing as an adaptive defence against viruses. Nature, 2001, 411, 834-842.
[18]
Hu, W.Y.; Myers, C.P.; Kilzer, J.M.; Pfaff, S.L.; Bushman, F.D. Inhibition of retroviral pathogenesis by RNA interference. Curr. Biol., 2002, 12(15), 1301-1311.
[http://dx.doi.org/10.1016/S0960-9822(02)00975-2] [PMID: 12176358]
[19]
Park, W.S.; Miyano-Kurosaki, N.; Hayafune, M.; Nakajima, E.; Matsuzaki, T.; Shimada, F.; Takaku, H. Prevention of HIV-1 infection in human peripheral blood mononuclear cells by specific RNA interference. Nucleic Acids Res., 2002, 30(22), 4830-4835.
[http://dx.doi.org/10.1093/nar/gkf627] [PMID: 12433985]
[20]
Elbashir, S.M.; Harborth, J.; Lendeckel, W.; Yalcin, A.; Weber, K.; Tuschl, T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature, 2001, 411(6836), 494-498.
[http://dx.doi.org/10.1038/35078107] [PMID: 11373684]
[21]
Surabhi, R.M.; Gaynor, R.B. RNA interference directed against viral and cellular targets inhibits human immunodeficiency Virus Type 1 replication. J. Virol., 2002, 76(24), 12963-12973.
[http://dx.doi.org/10.1128/JVI.76.24.12963-12973.2002] [PMID: 12438622]
[22]
Lee, N.S.; Dohjima, T.; Bauer, G.; Li, H.; Li, M.J.; Ehsani, A.; Salvaterra, P.; Rossi, J. Expression of small interfering RNAs targeted against HIV-1 rev transcripts in human cells. Nat. Biotechnol., 2002, 20(5), 500-505.
[http://dx.doi.org/10.1038/nbt0502-500] [PMID: 11981565]
[23]
Jacque, J.M.; Triques, K.; Stevenson, M. Modulation of HIV-1 replication by RNA interference. Nature, 2002, 418(6896), 435-438.
[http://dx.doi.org/10.1038/nature00896] [PMID: 12087358]
[24]
Das, A.T.; Brummelkamp, T.R.; Westerhout, E.M.; Vink, M.; Madiredjo, M.; Bernards, R.; Berkhout, B. Human immunodeficiency virus type 1 escapes from RNA interference-mediated inhibition. J. Virol., 2004, 78(5), 2601-2605.
[http://dx.doi.org/10.1128/JVI.78.5.2601-2605.2004] [PMID: 14963165]
[25]
Novina, C.D.; Murray, M.F.; Dykxhoorn, D.M.; Beresford, P.J.; Riess, J.; Lee, S.K.; Collman, R.G.; Lieberman, J.; Shankar, P.; Sharp, P.A. siRNA-directed inhibition of HIV-1 infection. Nat. Med., 2002, 8(7), 681-686.
[http://dx.doi.org/10.1038/nm725] [PMID: 12042777]
[26]
Martínez, M.A. Progress in the therapeutic applications of siRNAs against HIV-1. Methods Mol. Biol., 2009, 487, 343-368.
[http://dx.doi.org/10.1007/978-1-60327-547-7_17] [PMID: 19301656]
[27]
Zhou, J.; Wu, J.; Hafdi, N.; Behr, J.P.; Erbacher, P.; Peng, L. PAMAM dendrimers for efficient siRNA delivery and potent gene silencing. Chem. Commun.,, 2006, 2362-2364.
[28]
Rostami, B.; Irani, S.; Bolhassani, A.; Cohan, R.A. Gene and protein delivery using four cell penetrating peptides for HIV-1 vaccine development. IUBMB Life, 2019, 71(10), 1619-1633.
[http://dx.doi.org/10.1002/iub.2107] [PMID: 31220406]
[29]
Lavigne, C.; Slater, K.; Gajanayaka, N.; Duguay, C.; Arnau Peyrotte, E.; Fortier, G.; Simard, M.; Kell, A.J.; Barnes, M.L.; Thierry, A.R. Influence of lipoplex surface charge on siRNA delivery: application to the in vitro downregulation of CXCR4 HIV-1 co-receptor. Expert Opin. Biol. Ther., 2013, 13(7), 973-985.
[http://dx.doi.org/10.1517/14712598.2013.743526] [PMID: 23289797]
[30]
Mahajan, S.D.; Aalinkeel, R.; Reynolds, J.L.; Nair, B.; Sykes, D.E.; Law, W.C.; Ding, H.; Bergey, E.J.; Prasad, P.N.; Schwartz, S.A. Nanotherapeutics using an HIV-1 poly A and transactivator of the HIV-1 LTR (TAR-) specific siRNA. Pathol. Res. Int., 2011, 2011719139
[http://dx.doi.org/10.4061/2011/719139] [PMID: 21660279]
[31]
Weber, N.; Ortega, P.; Clemente, M.I.; Shcharbin, D.; Bryszewska, M.; de la Mata, F.J.; Gómez, R.; Muñoz-Fernández, M.A. Characterization of carbosilane dendrimers as effective carriers of siRNA to HIV-infected lymphocytes. J. Control. Release, 2008, 132(1), 55-64.
[http://dx.doi.org/10.1016/j.jconrel.2008.07.035] [PMID: 18727943]
[32]
Wrobel, D.; Kolanowska, K.; Gajek, A.; Gomez-Ramirez, R.; de la Mata, J.; Pedziwiatr-Werbicka, E.; Klajnert, B.; Waczulikova, I.; Bryszewska, M. Interaction of cationic carbosilane dendrimers and their complexes with siRNA with erythrocytes and red blood cell ghosts. Biochim. Biophys. Acta, 2014, 1838(3), 882-889.
[http://dx.doi.org/10.1016/j.bbamem.2013.11.017] [PMID: 24316171]
[33]
Jiménez, J.L.; Clemente, M.I.; Weber, N.D.; Sanchez, J.; Ortega, P.; de la Mata, F.J.; Gómez, R.; García, D.; López-Fernández, L.A.; Muñoz-Fernández, M.A. Carbosilane dendrimers to transfect human astrocytes with small interfering RNA targeting human immunodeficiency virus. BioDrugs, 2010, 24(5), 331-343.
[http://dx.doi.org/10.2165/11538400-000000000-00000] [PMID: 20795754]
[34]
Eszterhas, S.K.; Ilonzo, N.O.; Crozier, J.E.; Celaj, S.; Howell, A.L. Nanoparticles containing siRNA to silence CD4 and CCR5 reduce expression of these receptors and inhibit HIV-1 infection in human female reproductive tract tissue explants. Infect. Dis. Rep., 2011, 3(2)e11
[http://dx.doi.org/10.4081/idr.2011.2370] [PMID: 24470908]
[35]
Weber, N.D.; Merkel, O.M.; Kissel, T.; Muñoz-Fernández, M.Á. PEGylated poly(ethylene imine) copolymer-delivered siRNA inhibits HIV replication in vitro. J. Control. Release, 2012, 157(1), 55-63.
[http://dx.doi.org/10.1016/j.jconrel.2011.09.059] [PMID: 21930169]
[36]
Kim, S.H.; Jeong, J.H.; Ou, M.; Yockman, J.W.; Kim, S.W.; Bull, D.A. Cardiomyocyte-targeted siRNA delivery by prostaglandin E(2)-Fas siRNA polyplexes formulated with reducible poly(amido amine) for preventing cardiomyocyte apoptosis. Biomaterials, 2008, 29(33), 4439-4446.
[http://dx.doi.org/10.1016/j.biomaterials.2008.07.047] [PMID: 18725170]
[37]
Lee, J.M.; Yoon, T.J.; Cho, Y.S. Recent developments in nanoparticle-based siRNA delivery for cancer therapy. BioMed Res. Int., 2013, 2013782041
[http://dx.doi.org/10.1155/2013/782041] [PMID: 23844368]
[38]
Ding, Y.; Jiang, Z.; Saha, K.; Kim, C.S.; Kim, S.T.; Landis, R.F.; Rotello, V.M. Gold nanoparticles for nucleic acid delivery. Mol. Ther., 2014, 22(6), 1075-1083.
[http://dx.doi.org/10.1038/mt.2014.30] [PMID: 24599278]
[39]
Liu, Z.; Winters, M.; Holodniy, M.; Dai, H. siRNA delivery into human T cells and primary cells with carbon-nanotube transporters. Angew. Chem. Int. Ed. Engl., 2007, 46(12), 2023-2027.
[http://dx.doi.org/10.1002/anie.200604295] [PMID: 17290476]
[40]
Zhou, J.; Swiderski, P.; Li, H.; Zhang, J.; Neff, C.P.; Akkina, R.; Rossi, J.J. Selection, characterization and application of new RNA HIV gp 120 aptamers for facile delivery of Dicer substrate siRNAs into HIV infected cells. Nucleic Acids Res., 2009, 37(9), 3094-3109.
[http://dx.doi.org/10.1093/nar/gkp185] [PMID: 19304999]
[41]
Zhou, J.; Li, H.; Li, S.; Zaia, J.; Rossi, J.J. Novel dual inhibitory function aptamer-siRNA delivery system for HIV-1 therapy. Mol. Ther., 2008, 16(8), 1481-1489.
[http://dx.doi.org/10.1038/mt.2008.92] [PMID: 18461053]
[42]
Dove, A. An apt approach. Nat. Med., 2010, 16(3), 258-260.
[http://dx.doi.org/10.1038/nm0310-258] [PMID: 20208504]
[43]
Kim, D.H.; Longo, M.; Han, Y.; Lundberg, P.; Cantin, E.; Rossi, J.J. Interferon induction by siRNAs and ssRNAs synthesized by phage polymerase. Nat. Biotechnol., 2004, 22(3), 321-325.
[http://dx.doi.org/10.1038/nbt940] [PMID: 14990954]
[44]
Takahashi, M.; Burnett, J.C.; Rossi, J.J. Aptamer-siRNA chimeras for HIV. Adv. Exp. Med. Biol., 2015, 848, 211-234.
[http://dx.doi.org/10.1007/978-1-4939-2432-5_11] [PMID: 25757623]
[45]
Boyapalle, S.; Xu, W.; Raulji, P.; Mohapatra, S.; Mohapatra, S.S. A multiple siRNA-based anti-HIV/SHIV microbicide shows protection in both in vitro and in vivo models. PLoS One, 2015, 10(9)e0135288
[http://dx.doi.org/10.1371/journal.pone.0135288] [PMID: 26407080]
[46]
Gu, J.; Al-Bayati, K.; Ho, E.A. Development of antibody-modified chitosan nanoparticles for the targeted delivery of siRNA across the blood-brain barrier as a strategy for inhibiting HIV replication in astrocytes. Drug Deliv. Transl. Res., 2017, 7(4), 497-506.
[http://dx.doi.org/10.1007/s13346-017-0368-5] [PMID: 28315051]
[47]
Zhou, J.; Neff, C.P.; Swiderski, P.; Li, H.; Smith, D.D.; Aboellail, T.; Remling-Mulder, L.; Akkina, R.; Rossi, J.J. Functional in vivo delivery of multiplexed anti-HIV-1 siRNAs via a chemically synthesized aptamer with a sticky bridge. Mol. Ther., 2013, 21(1), 192-200.
[http://dx.doi.org/10.1038/mt.2012.226] [PMID: 23164935]
[48]
Mizrahy, S.; Hazan-Halevy, I.; Dammes, N.; Landesman-Milo, D.; Peer, D. Current progress in non-viral RNAi-based delivery strategies to lymphocytes. Molecular Therapy,, 2017, 25(7), 1491-1500.
[49]
Zhou, J.; Lazar, D.; Li, H.; Xia, X.; Satheesan, S.; Charlins, P.; O’Mealy, D.; Akkina, R.; Saayman, S.; Weinberg, M.S.; Rossi, J.J.; Morris, K.V. Receptor-targeted aptamer-siRNA conjugate-directed transcriptional regulation of HIV-1. Theranostics, 2018, 8(6), 1575-1590.
[http://dx.doi.org/10.7150/thno.23085] [PMID: 29556342]
[50]
Rodriguez, M.; Lapierre, J.; Ojha, C.R.; Kaushik, A.; Batrakova, E.; Kashanchi, F.; Dever, S.M.; Nair, M.; El-Hage, N. Intranasal drug delivery of small interfering RNA targeting Beclin1 encapsulated with polyethylenimine (PEI) in mouse brain to achieve HIV attenuation. Sci. Rep., 2017, 7(1), 1862.
[http://dx.doi.org/10.1038/s41598-017-01819-9] [PMID: 28500326]
[51]
Zhou, J.; Neff, C.P.; Liu, X.; Zhang, J.; Li, H.; Smith, D.D.; Swiderski, P.; Aboellail, T.; Huang, Y.; Du, Q.; Liang, Z.; Peng, L.; Akkina, R.; Rossi, J.J. Systemic administration of combinatorial dsiRNAs via nanoparticles efficiently suppresses HIV-1 infection in humanized mice. Mol. Ther., 2011, 19(12), 2228-2238.
[http://dx.doi.org/10.1038/mt.2011.207] [PMID: 21952167]
[52]
Blakney, A.K.; McKay, P.F.; Yus, B.I.; Aldon, Y.; Shattock, R.J. Inside out: optimization of lipid nanoparticle formulations for exterior complexation and in vivo delivery of saRNA. Gene Ther., 2019, 26(9), 363-372.
[http://dx.doi.org/10.1038/s41434-019-0095-2] [PMID: 31300730]
[53]
Song, E.; Zhu, P.; Lee, S.K.; Chowdhury, D.; Kussman, S.; Dykxhoorn, D.M.; Feng, Y.; Palliser, D.; Weiner, D.B.; Shankar, P.; Marasco, W.A.; Lieberman, J. Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors. Nat. Biotechnol., 2005, 23(6), 709-717.
[http://dx.doi.org/10.1038/nbt1101] [PMID: 15908939]
[54]
Reynolds, J.L.; Law, W.C.; Mahajan, S.D.; Aalinkeel, R.; Nair, B.; Sykes, D.E.; Yong, K.T.; Hui, R.; Prasad, P.N.; Schwartz, S.A. Nanoparticle based galectin-1 gene silencing, implications in methamphetamine regulation of HIV-1 infection in monocyte derived macrophages. J. Neuroimmune Pharmacol., 2012, 7(3), 673-685.
[http://dx.doi.org/10.1007/s11481-012-9379-7] [PMID: 22689223]
[55]
Nozari, A.; Berezovski, M.V. Aptamers for CD antigens: From cell profiling to activity modulation. Mol. Ther. Nucleic Acids, 2017, 6, 29-44.
[http://dx.doi.org/10.1016/j.omtn.2016.12.002] [PMID: 28325295]
[56]
Lakhin, A.V.; Tarantul, V.Z.; Gening, L.V. Aptamers: problems, solutions and prospects. Acta Naturae, 2013, 5(4), 34-43.
[http://dx.doi.org/10.32607/20758251-2013-5-4-34-43] [PMID: 24455181]
[57]
Capodici, J.; Karikó, K.; Weissman, D. Inhibition of HIV-1 infection by small interfering RNA-mediated RNA interference. J. Immunol., 2002, 169(9), 5196-5201.
[http://dx.doi.org/10.4049/jimmunol.169.9.5196] [PMID: 12391237]
[58]
Gu, J.; Yang, S.; Ho, E.A. Biodegradable film for the targeted delivery of siRNA-loaded nanoparticles to vaginal immune cells. Mol. Pharm., 2015, 12(8), 2889-2903.
[http://dx.doi.org/10.1021/acs.molpharmaceut.5b00073] [PMID: 26099315]
[59]
Yan, M.; Liang, M.; Wen, J.; Liu, Y.; Lu, Y.; Chen, I.S.Y. Single siRNA nanocapsules for enhanced RNAi delivery. J. Am. Chem. Soc., 2012, 134(33), 13542-13545.
[http://dx.doi.org/10.1021/ja304649a] [PMID: 22866878]
[60]
Peng, J.; Wu, Z.; Qi, X.; Chen, Y.; Li, X. Dendrimers as potential therapeutic tools in HIV inhibition. Molecules, 2013, 18, 7912-7929.
[61]
Shcharbin, D.; Pedziwiatr, E.; Nowacka, O.; Kumar, M.; Zaborski, M.; Ortega, P.; de la Mata, F.J.; Gómez, R.; Muñoz-Fernandez, M.A.; Bryszewska, M. Carbosilane dendrimers NN8 and NN16 form a stable complex with siGAG1. Colloids Surf. B Biointerfaces, 2011, 83(2), 388-391.
[http://dx.doi.org/10.1016/j.colsurfb.2010.11.009] [PMID: 21145713]
[62]
Ionov, M.; Garaiova, Z.; Waczulikova, I.; Wróbel, D.; Pędziwiatr-Werbicka, E.; Gomez-Ramirez, R.; de la Mata, F.J.; Klajnert, B.; Hianik, T.; Bryszewska, M. siRNA carriers based on carbosilane dendrimers affect zeta potential and size of phospholipid vesicles. Biochim. Biophys. Acta, 2012, 1818(9), 2209-2216.
[http://dx.doi.org/10.1016/j.bbamem.2012.04.019] [PMID: 22575422]
[63]
Briz, V.; Serramía, M.J.; Madrid, R.; Hameau, A.; Caminade, A.M.; Majoral, J.P.; Muñoz-Fernández, M.A. Validation of a generation 4 phosphorus-containing polycationic dendrimer for gene delivery against HIV-1. Curr. Med. Chem., 2012, 19(29), 5044-5051.
[http://dx.doi.org/10.2174/0929867311209025044] [PMID: 22963636]
[64]
Perisé-Barrios, A.J.; Jiménez, J.L.; Domínguez-Soto, A.; de la Mata, F.J.; Corbí, A.L.; Gomez, R.; Muñoz-Fernandez, M.Á. Carbosilane dendrimers as gene delivery agents for the treatment of HIV infection. J. Control. Release, 2014, 184, 51-57.
[http://dx.doi.org/10.1016/j.jconrel.2014.03.048] [PMID: 24721235]
[65]
Sánchez-Nieves, J.; Fransen, P.; Pulido, D.; Lorente, R.; Muñoz-Fernández, M.A.; Albericio, F.; Royo, M.; Gómez, R.; de la Mata, F.J. Amphiphilic cationic carbosilane-PEG dendrimers: synthesis and applications in gene therapy. Eur. J. Med. Chem., 2014, 76, 43-52.
[http://dx.doi.org/10.1016/j.ejmech.2014.01.061] [PMID: 24565572]
[66]
Serramía, M.J.; Álvarez, S.; Fuentes-Paniagua, E.; Clemente, M.I.; Sánchez-Nieves, J.; Gómez, R.; de la Mata, J.; Muñoz-Fernández, M.A. In vivo delivery of siRNA to the brain by carbosilane dendrimer. J. Control. Release, 2015, 200, 60-70.
[http://dx.doi.org/10.1016/j.jconrel.2014.12.042] [PMID: 25559178]
[67]
Kumar, P.; Ban, H.S.; Kim, S.S.; Wu, H.; Pearson, T.; Greiner, D.L.; Laouar, A.; Yao, J.; Haridas, V.; Habiro, K.; Yang, Y.G.; Jeong, J.H.; Lee, K.Y.; Kim, Y.H.; Kim, S.W.; Peipp, M.; Fey, G.H.; Manjunath, N.; Shultz, L.D.; Lee, S.K.; Shankar, P. T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice. Cell, 2008, 134(4), 577-586.
[http://dx.doi.org/10.1016/j.cell.2008.06.034] [PMID: 18691745]
[68]
Zhou, J.; Shu, Y.; Guo, P.; Smith, D.D.; Rossi, J.J. Dual functional RNA nanoparticles containing phi29 motor pRNA and anti-gp120 aptamer for cell-type specific delivery and HIV-1 inhibition. Methods, 2011, 54(2), 284-294.
[http://dx.doi.org/10.1016/j.ymeth.2010.12.039] [PMID: 21256218]
[69]
Neff, C.P.; Zhou, J.; Remling, L.; Kuruvilla, J.; Zhang, J.; Li, H.; Smith, D.D.; Swiderski, P.; Rossi, J.J.; Akkina, R. An aptamer-siRNA chimera suppresses HIV-1 viral loads and protects from helper CD4(+) T cell decline in humanized mice. Sci. Transl. Med., 2011, 3(66), 66ra6.
[http://dx.doi.org/10.1126/scitranslmed.3001581] [PMID: 21248316]


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VOLUME: 13
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Year: 2020
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DOI: 10.2174/1874467212666191023120954
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