Viral vectors have been extensively studied due to their great transduction efficiency compared to non-viral vectors. These vectors have been used extensively in gene therapy, enabling the comprehension of, not only the advantages of these vectors, but also the limitations, such as the activation of the immune system after vector administration. Moreover, the need to control the target of the vector has led to the development of chemical and non-chemical modifications of the vector surface, allowing researchers to modify the tropism and biodistribution profile of the vector, leading to the production of viral vectors able to target different tissues and organs. This review describes recent non-genetic modifications of the surfaces of viral vectors to decrease immune system activation and to control tissue targeting. The developments described herein provide opportunities for applications of gene therapy to treat acquired disorders and genetic diseases and to become useful tools in regenerative medicine.
References
[1]
Kay, A.M.; Glorioso, G.; Naldini, L. Viral vectors for gene therapy: The art of turning infectious agents into vehicles of therapeutics. Nat. Med. 2001, 7, 33–40, doi:10.1038/83324.
[2]
Young, L.S.; Searle, P.F.; Onion, D.; Mautner, V. Viral gene therapy strategies: From basic science to clinical application. J. Pathol. 2006, 208, 299–318, doi:10.1002/path.1896.
[3]
Escors, D.; Breckpot, K. Lentiviral vectors in gene therapy: Their current status and future potential. Arch. Immunol. Ther. Exp. 2010, 58, 107–119, doi:10.1007/s00005-010-0063-4.
[4]
Palmer, D.J.; Ng, P. Characterization of helper-dependent adenoviral vectors. Cold Spring Harb. Protoc. 2011, 2011, 867–870.
[5]
Brunetti-Pierri, N.; Ng, P. Helper-dependent adenoviral vectors for liver-directed gene therapy. Hum. Mol. Genet. 2011, 20, R7–R13, doi:10.1093/hmg/ddr143.
[6]
Cooray, S.; Howe, S.J.; Thrasher, A.J. Retrovirus and lentivirus vector design and methods of cell conditioning. Methods Enzymol. 2012, 507, 29–57.
[7]
Miyoshi, H.; Blomer, U.; Takahashi, M.; Gage, F.H.; Verma, I.M. Development of a self-inactivating lentivirus vector. J. Virol. 1998, 72, 8150–8157.
[8]
Brunetti-Pierri, N.; Palmer, D.J.; Beaudet, A.L.; Carey, K.D.; Finegold, M.; Ng, P. Acute toxicity after high-dose systemic injection of helper-dependent adenoviral vectors into nonhuman primates. Hum. Gene Ther. 2004, 15, 35–46, doi:10.1089/10430340460732445.
Seiler, M.P.; Cerullo, V.; Lee, B. Immune response to helper dependent adenoviral mediated liver gene therapy: Challenges and prospects. Curr. Gene Ther. 2007, 7, 297–305, doi:10.2174/156652307782151452.
[14]
Breckpot, K.; Escors, D.; Arce, F.; Lopes, L.; Karwacz, K.; van Lint, S.; Keyaerts, M.; Collins, M. HIV-1 lentiviral vector immunogenicity is mediated by toll-like receptor 3 (TLR3) and TLR7. J. Virol. 2010, 84, 5627–5636.
[15]
Suzuki, M.; Cerullo, V.; Bertin, T.K.; Cela, R.; Clarke, C.; Guenther, M.; Brunetti-Pierri, N.; Lee, B. Myd88-dependent silencing of transgene expression during the innate and adaptive immune response to helper-dependent adenovirus. Hum. Gene Ther. 2010, 21, 325–336, doi:10.1089/hum.2009.155.
[16]
Rhee, E.G.; Blattman, J.N.; Kasturi, S.P.; Kelley, R.P.; Kaufman, D.R.; Lynch, D.M.; La Porte, A.; Simmons, N.L.; Clark, S.L.; Pulendran, B.; et al. Multiple innate immune pathways contribute to the immunogenicity of recombinant adenovirus vaccine vectors. J. Virol. 2011, 85, 315–323, doi:10.1128/JVI.01597-10.
[17]
Pradere, J.P.; Dapito, D.H.; Schwabe, R.F. The yin and yang of toll-like receptors in cancer. Oncogene 2013, doi:10.1038/onc.2013.302.
Bayo-Puxan, N.; Gimenez-Alejandre, M.; Lavilla-Alonso, S.; Gros, A.; Cascallo, M.; Hemminki, A.; Alemany, R. Replacement of adenovirus type 5 fiber shaft heparan sulfate proteoglycan-binding domain with RGD for improved tumor infectivity and targeting. Hum. Gene Ther. 2009, 20, 1214–1221, doi:10.1089/hum.2009.038.
Schulte, M.; Sorkin, M.; Al-Benna, S.; Stupka, J.; Hirsch, T.; Daigeler, A.; Kesting, M.R.; Steinau, H.U.; Jacobsen, F.; Steinstraesser, L. Innate immune response after adenoviral gene delivery into skin is mediated by AIM2, NALP3, DAI and MDA5. SpringerPlus 2013, 2, 234, doi:10.1186/2193-1801-2-234.
[23]
Veronese, F.M.; Mero, A. The impact of pegylation on biological therapies. Biodrugs 2008, 22, 315–329, doi:10.2165/00063030-200822050-00004.
[24]
Croyle, M.A.; Le, H.T.; Linse, K.D.; Cerullo, V.; Toietta, G.; Beaudet, A.; Pastore, L. Pegylated helper-dependent adenoviral vectors: Highly efficient vectors with an enhanced safety profile. Gene Ther. 2005, 12, 579–587, doi:10.1038/sj.gt.3302441.
[25]
Wonganan, P.; Croyle, M.A. Pegylated adenoviruses: From mice to monkeys. Viruses 2010, 2, 468–502, doi:10.3390/v2020468.
[26]
Tesfay, M.Z.; Kirk, A.C.; Hadac, E.M.; Griesmann, G.E.; Federspiel, M.J.; Barber, G.N.; Henry, S.M.; Peng, K.W.; Russell, S.J. Pegylation of vesicular stomatitis virus extends virus persistence in blood circulation of passively immunized mice. J. Virol. 2013, 87, 3752–3759, doi:10.1128/JVI.02832-12.
[27]
Alemany, R.; Suzuki, K.; Curiel, D.T. Blood clearance rates of adenovirus type 5 in mice. J. Gen. Virol. 2000, 81, 2605–2609.
[28]
Metzner, C.; Kochan, F.; Dangerfield, J.A. Postexit surface engineering of retroviral/lentiviral vectors. BioMed Res. Int. 2013, 2013, 253521:1–253521:8.
[29]
Leggiero, E.; Astone, D.; Cerullo, V.; Lombardo, B.; Mazzaccara, C.; Labruna, G.; Sacchetti, L.; Salvatore, F.; Croyle, M.; Pastore, L. Pegylated helper-dependent adenoviral vector expressing human Apo A-I for gene therapy in ldlr-deficient mice. Gene Ther. 2013, doi:10.1038/gt.2013.38.
[30]
Kreppel, F.; Kochanek, S. Modification of adenovirus gene transfer vectors with synthetic polymers: A scientific review and technical guide. Mol. Ther. 2008, 16, 16–29, doi:10.1038/sj.mt.6300321.
[31]
Eto, Y.; Yoshioka, Y.; Ishida, T.; Yao, X.; Morishige, T.; Narimatsu, S.; Mizuguchi, H.; Mukai, Y.; Okada, N.; Kiwada, H.; et al. Optimized pegylated adenovirus vector reduces the anti-vector humoral immune response against adenovirus and induces a therapeutic effect against metastatic lung cancer. Biol. Pharm. Bull. 2010, 33, 1540–1544, doi:10.1248/bpb.33.1540.
Croyle, M.A.; Callahan, S.M.; Auricchio, A.; Schumer, G.; Linse, K.D.; Wilson, J.M.; Brunner, L.J.; Kobinger, G.P. PEGylation of a vesicular stomatitis virus G pseudotyped lentivirus vector prevents inactivation in serum. J. Virol. 2003, 78, 912–921.
[34]
Ahn, C.H.; Chae, S.Y.; Bae, Y.H.; Kim, S.W. Synthesis of biodegradable multi-block copolymers of poly(l-lysine) and poly(ethylene glycol) as a non-viral gene carrier. J. Control. Release 2004, 97, 567–574.
[35]
Zeng, Q.; Han, J.; Zhao, D.; Gong, T.; Zhang, Z.; Sun, X. Protection of adenovirus from neutralizing antibody by cationic PEG derivative ionically linked to adenovirus. Int. J. Nanomed. 2012, 7, 985–997.
[36]
Fisher, K.D.; Seymour, L.W. HPMA copolymers for masking and retargeting of therapeutic viruses. Adv. Drug Deliv. Rev. 2010, 62, 240–245, doi:10.1016/j.addr.2009.12.003.
[37]
Wang, C.H.; Chan, L.W.; Johnson, R.N.; Chu, D.S.; Shi, J.; Schellinger, J.G.; Lieber, A.; Pun, S.H. The transduction of coxsackie and adenovirus receptor-negative cells and protection against neutralizing antibodies by HPMA-co-oligolysine copolymer-coated adenovirus. Biomaterials 2011, 32, 9536–9545, doi:10.1016/j.biomaterials.2011.08.069.
[38]
Kim, P.H.; Kim, J.; Kim, T.I.; Nam, H.Y.; Yockman, J.W.; Kim, M.; Kim, S.W.; Yun, C.O. Bioreducible polymer-conjugated oncolytic adenovirus for hepatoma-specific therapy via systemic administration. Biomaterials 2011, 32, 9328–9342, doi:10.1016/j.biomaterials.2011.08.066.
[39]
Singh, R.; Al-Jamal, K.T.; Lacerda, L.; Kostarelos, K. Nanoengineering artificial lipid envelopes around adenovirus by self-assembly. ACS Nano 2008, 2, 1040–1050, doi:10.1021/nn8000565.
[40]
Yilmazer, A.; Al-Jamal, W.T.; van den Bossche, J.; Kostarelos, K. The effect of artificial lipid envelopment of adenovirus 5 (ad5) on liver de-targeting and hepatotoxicity. Biomaterials 2013, 34, 1354–1363, doi:10.1016/j.biomaterials.2012.10.053.
[41]
Bergelson, J.M.; Cunningham, J.A.; Droguett, G.; Kurt-Jones, E.A.; Krithivas, A.; Hong, J.S.; Horwitz, M.S.; Crowell, R.L.; Finberg, R.W. Isolation of a common receptor for coxsackie b viruses and adenoviruses 2 and 5. Science 1997, 275, 1320–1323, doi:10.1126/science.275.5304.1320.
[42]
Hastie, E.; Cataldi, M.; Marriott, I.; Grdzelishvili, V.Z. Understanding and altering cell tropism of vesicular stomatitis virus. Virus Res. 2013, 176, 16–32, doi:10.1016/j.virusres.2013.06.003.
[43]
Finkelshtein, D.; Werman, A.; Novick, D.; Barak, S.; Rubinstein, M. LDL receptor and its family members serve as the cellular receptors for vesicular stomatitis virus. Proc. Natl. Acad. Sci. USA 2013, 110, 7306–7311.
[44]
Glazkova, D.V.; Vetchinova, A.S.; Bogoslovskaia, E.V.; Zhogina, Y.A.; Markelov, M.L.; Shipulin, G.A. Downregulation of human CCR5 receptor gene expression using artificial microRNAs. Mol. Biol. 2013, 47, 419–428, doi:10.1134/S0026893313030035.
[45]
Martin, K.; Brie, A.; Saulnier, P.; Perricaudet, M.; Yeh, P.; Vigne, E. Simultaneous car- and alpha v integrin-binding ablation fails to reduce ad5 liver tropism. Mol. Ther. 2003, 8, 485–494, doi:10.1016/S1525-0016(03)00182-5.
Wonganan, P.; Clemens, C.C.; Brasky, K.; Pastore, L.; Croyle, M.A. Species differences in the pharmacology and toxicology of PEGylated helper-dependent adenovirus. Mol. Pharm. 2011, 8, 78–92, doi:10.1021/mp100216h.
Doronin, K.; Shashkova, E.V.; May, S.M.; Hofherr, S.E.; Barry, M.A. Chemical modification with high molecular weight polyethylene glycol reduces transduction of hepatocytes and increases efficacy of intravenously delivered oncolytic adenovirus. Hum. Gene Ther. 2009, 20, 975–988, doi:10.1089/hum.2009.028.
[50]
Mok, H.; Palmer, D.J.; Ng, P.; Barry, M.A. Evaluation of polyethylene glycol modification of first-generation and helper-dependent adenoviral vectors to reduce innate immune responses. Mol. Ther. 2005, 11, 66–79.
[51]
Hofherr, S.E.; Shashkova, E.V.; Weaver, E.A.; Khare, R.; Barry, M.A. Modification of adenoviral vectors with polyethylene glycol modulates in vivo tissue tropism and gene expression. Mol. Ther. 2008, 16, 1276–1282, doi:10.1038/mt.2008.86.
Wang, I.J.; Jhuang, M.C.; Chen, Y.H.; Yeh, L.K.; Liu, C.Y.; Young, T.H. Chitosan modification of adenovirus to modify transfection efficiency in bovine corneal epithelial cells. PLoS One 2010, 5, e12085.
[54]
Kang, S.H.; Zirbes, E.L.; Kole, R. Delivery of antisense oligonucleotides and plasmid DNA with various carrier agents. Antisense Nucleic Acid Drug Dev. 1999, 9, 497–505, doi:10.1089/oli.1.1999.9.497.
[55]
Vetter, A.; Virdi, K.S.; Espenlaub, S.; Rodl, W.; Wagner, E.; Holm, P.S.; Scheu, C.; Kreppel, F.; Spitzweg, C.; Ogris, M. Adenoviral vectors coated with PAMAM dendrimer conjugates allow car independent virus uptake and targeting to the egf receptor. Mol. Pharm. 2013, 10, 606–618, doi:10.1021/mp300366f.
[56]
Pandori, M.W.; Hobson, D.A.; Sano, T. Adenovirus-microbead conjugates possess enhanced infectivity: A new strategy for localized gene delivery. Virology 2002, 299, 204–212, doi:10.1006/viro.2002.1510.
Sapet, C.; Pellegrino, C.; Laurent, N.; Sicard, F.; Zelphati, O. Magnetic nanoparticles enhance adenovirus transduction in vivo and in vivo. Pharm. Res. 2012, 29, 1203–1218, doi:10.1007/s11095-011-0629-9.
[59]
Hoffman, J.A.; Giraudo, E.; Singh, M.; Zhang, L.; Inoue, M.; Porkka, K.; Hanahan, D.; Ruoslahti, E. Progressive vascular changes in a transgenic mouse model of squamous cell carcinoma. Cancer Cell 2003, 4, 383–391, doi:10.1016/S1535-6108(03)00273-3.
[60]
Yao, X.L.; Yoshioka, Y.; Ruan, G.X.; Chen, Y.Z.; Mizuguchi, H.; Mukai, Y.; Okada, N.; Gao, J.Q.; Nakagawa, S. Optimization and internalization mechanisms of PEGylated adenovirus vector with targeting peptide for cancer gene therapy. Biomacromolecules 2012, 13, 2402–2409, doi:10.1021/bm300665u.
[61]
Yao, X.; Yoshioka, Y.; Morishige, T.; Eto, Y.; Narimatsu, S.; Kawai, Y.; Mizuguchi, H.; Gao, J.Q.; Mukai, Y.; Okada, N.; et al. Tumor vascular targeted delivery of polymer-conjugated adenovirus vector for cancer gene therapy. Mol. Ther. 2011, 19, 1619–1625, doi:10.1038/mt.2011.112.
[62]
Xiong, Z.; Cheng, Z.; Zhang, X.; Patel, M.; Wu, J.C.; Gambhir, S.S.; Chen, X. Imaging chemically modified adenovirus for targeting tumors expressing integrin alphavbeta3 in living mice with mutant herpes simplex virus type 1 thymidine kinase pet reporter gene. J. Nucl. Med. 2006, 47, 130–139.
[63]
King, W.J.; Krebsbach, P.H. Cyclic-RGD peptides increase the adenoviral transduction of human mesenchymal stem cells. Stem Cells Dev. 2013, 22, 679–686, doi:10.1089/scd.2012.0379.
Bonsted, A.; Engesaeter, B.O.; Hogset, A.; Maelandsmo, G.M.; Prasmickaite, L.; D’Oliveira, C.; Hennink, W.E.; van Steenis, J.H.; Berg, K. Photochemically enhanced transduction of polymer-complexed adenovirus targeted to the epidermal growth factor receptor. J. Gene Med. 2006, 8, 286–297, doi:10.1002/jgm.853.
[66]
Morrison, J.; Briggs, S.S.; Green, N.; Fisher, K.; Subr, V.; Ulbrich, K.; Kehoe, S.; Seymour, L.W. Virotherapy of ovarian cancer with polymer-cloaked adenovirus retargeted to the epidermal growth factor receptor. Mol. Ther. 2008, 16, 244–251, doi:10.1038/sj.mt.6300363.
[67]
Paul, A.; Shao, W.; Abbasi, S.; Shum-Tim, D.; Prakash, S. Pamam dendrimer-baculovirus nanocomplex for microencapsulated adipose stem cell-gene therapy: In vitro and in vivo functional assessment. Mol. Pharm. 2012, 9, 2479–2488, doi:10.1021/mp3000502.
[68]
Grunwald, G.K.; Vetter, A.; Klutz, K.; Willhauck, M.J.; Schwenk, N.; Senekowitsch-Schmidtke, R.; Schwaiger, M.; Zach, C.; Wagner, E.; Goke, B.; et al. Systemic image-guided liver cancer radiovirotherapy using dendrimer-coated adenovirus encoding the sodium iodide symporter as theranostic gene. J. Nucl. Med. 2013, 54, 1450–1457, doi:10.2967/jnumed.112.115493.
[69]
Walters, C.L.; Arend, R.C.; Armstrong, D.K.; Naumann, R.W.; Alvarez, R.D. Folate and folate receptor alpha antagonists mechanism of action in ovarian cancer. Gynecol. Oncol. 2013, 131, 493–498, doi:10.1016/j.ygyno.2013.07.080.
[70]
Xie, M.; Zhang, H.; Xu, Y.; Liu, T.; Chen, S.; Wang, J.; Zhang, T. Expression of folate receptors in nasopharyngeal and laryngeal carcinoma and folate receptor-mediated endocytosis by molecular targeted nanomedicine. Int. J. Nanomed. 2013, 8, 2443–2451.
[71]
Reddy, J.A.; Clapp, D.W.; Low, P.S. Retargeting of viral vectors to the folate receptor endocytic pathway. J. Control. Release 2001, 74, 77–82, doi:10.1016/S0168-3659(01)00316-9.
[72]
Kwon, O.J.; Kang, E.; Choi, J.W.; Kim, S.W.; Yun, C.O. Therapeutic targeting of chitosan-peg-folate-complexed oncolytic adenovirus for active and systemic cancer gene therapy. J. Control. Release 2013, 169, 257–265, doi:10.1016/j.jconrel.2013.03.030.
Green, N.K.; Morrison, J.; Hale, S.; Briggs, S.S.; Stevenson, M.; Subr, V.; Ulbrich, K.; Chandler, L.; Mautner, V.; Seymour, L.W.; et al. Retargeting polymer-coated adenovirus to the FGF receptor allows productive infection and mediates efficacy in a peritoneal model of human ovarian cancer. J. Gene Med. 2008, 10, 280–289, doi:10.1002/jgm.1121.