Methods of gene delivery and perspectives of their application in the gene therapy

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access


Gene therapy is believed to be among the most promising directions of the future medicine. Thus, the development of efficient and safe methods of the nucleic acid delivery to the target cells, tissues and organs ecomes of great current interest. This review summarizes recent data on the approaches for the gene delivery and discusses clinical aspects of the gene therapy.

Full Text

Restricted Access

About the authors

E. K Apartsin

Institute of Chemical Biology and Fundamental Medicine, the Siberian Branch of the Russian Academy of Sciences

Novosibirsk, Russia

N. Yu Knauer

Research Institute of Fundamental and Clinical Immunology

Novosibirsk, Russia


  1. Petrus I., Chuah M., van den Driessche T. Gene therapy strategies for hemophilia: benefits versus risks. J. Gene Med. 2010; 12: 797-809.
  2. Kay M.A. State-of-the-art gene-based therapies: the road ahead. Nat. Rev. Genet. 2011; 12: 316-28.
  3. Wasala N.B., Shin J.H., Duan D. The evolution of heart gene delivery vectors. J. Gene Med. 2011; 13: 557-65.
  4. Parker A.L., Nicklin S.A., Baker A.H. Interactions of adenovirus vectors with blood: implications for intravascular gene therapy applications. Curr. Opin. Mol. Ther. 2008; 10: 439-48.
  5. Du L., Dronadula N., Tanaka S. et al. Helper-dependent adenoviral vector achieves prolonged, stable expression of interleukin-10 in rabbit carotid arteries but does not limit early atherogenesis. Hum. Gene Ther. 2011; 22: 959-68.
  6. Chuah M.K.L., Collen D., van den Driessche T. Biosafety of adenoviral vectors. Curr. Gene Ther. 2003; 3: 527-43.
  7. Lentz T.B., Gray S.J., Samulski R.J. Viral vectors for gene delivery to the central nervous system. Neurobiol. Disease 2012; 48: 179-88.
  8. Rey-Rico A., Cucchiarini M. Controlled release strategies for rAAV-mediated gene delivery Acta Biomater. 2016; 29: 1-10.
  9. Ibraheem D., Elaissari A., Fessi H. Gene therapy and DNA delivery systems. Int. J. Pharm. 2014; 459: 70-83.
  10. Ojala D.S., Amara D.P., Schaffer D.V. Adeno-associated virus vectors and neurological gene therapy. Neuroscientist 2015; 21: 84-98.
  11. Rivera V.M., Gao G.P., Grant R.L. et al. Long-term pharmacologically regulated expression of erythropoietin in primates following AAV-mediated gene transfer. Blood 2005; 105: 1424-30.
  12. Niemeyer G.P., Herzog R.W., Mount J. et al. Long-term correction of inhibitor-prone hemophilia B dogs treated with liverdirected AAV2-mediated factor IX gene therapy. Blood 2009; 113: 797-806.
  13. Stieger K., Schroeder J., Provost N. et al. Detection of intact rAAV particles up to 6 years after successful gene transfer in the retina of dogs and primates. Mol. Ther. 2009; 17: 516-23.
  14. Leone P., Shera D., McPhee S.W. et al. Long-term follow-up after gene therapy for canavan disease. Science Transl. Med. 2012; 4: 165ra163.
  15. Vandenberghe L.H., Wilson J.M. AAV as an immunogen. Curr. Gene Ther. 2007; 7: 325-33.
  16. Baum C., Schambach A., Bohne J. et al. Retrovirus vectors: toward the plentivirus? Mol. Ther. 2006; 13: 1050-63.
  17. Cooray S., Howe S.J., Thrasher A.J. Retrovirus and lentivirus vector design and methods of cell conditioning. Methods Enzymol. 2012; 507: 29-57.
  18. Suzuki Y., Craigie R. The road to chromatin - nuclear entry of retroviruses. Nat. Rev. Microbiol. 2007; 5: 187-96.
  19. Seidlits S.K., Gower R.M., Shepard J.A. et al. Hydrogels for lentiviral gene delivery. Expert Opin. Drug Deliv. 2013; 10: 499-509.
  20. Matrai J., Chuah M.K.L., van den Driessche T. Recent advances in lentiviral vector development and applications. Mol. Ther. 2010; 18: 477-90.
  21. Sakuma T., Barry M.A., Ikeda Y. Lentiviral vectors: basic to translational. Biochem. J. 2012; 443: 603-18.
  22. Dull T., Zufferey R., Kelly M. et al. A third-generation lentivirus vector with a conditional packaging system. J. Virol. 1998; 72: 8463-71.
  23. Zhang X., Godbey W. Viral vectors for gene delivery in tissue engineering. Adv. Drug Deliv. Rev. 2006; 58: 515-34.
  24. Papayannakos C., Daniel R. Understanding lentiviral vector chromatin targeting: working to reduce insertional mutagenic potential for gene therapy. Gene Ther. 2013; 20: 581-8.
  25. Kantor B., Bailey R.M., Wimberly K. et al. Methods for gene transfer to the central nervous system. Adv. Genet. 2014; 87: 125-97.
  26. Lundstrom K. Alphaviruses in gene therapy. Viruses 2015; 7: 2321-33.
  27. Makkonen K.E., Airenne K., Ylä-Herttulala S. Baculovirus-mediated gene delivery and RNAi applications. Viruses 2015; 7: 2099-125.
  28. Airenne K.J., Hu Y.C., Kost T.A. et al. Baculovirus: an insect-derived vector for diverse gene transfer applications. Mol. Ther. 2013; 21: 739-49.
  29. Bakhshinejad B., Sadeghizadeh M. Bacteriophages as vehicles for gene delivery into mammalian cells: prospects and problems. Expert Opin. Drug Deliv. 2014; 11:1561-74.
  30. Buchholz C.J., Friedel T., Büning H. Surface-engineered viral vectors for selective and cell type-specific gene delivery. Trends Biotechnol. 2015; 33: 777-90.
  31. Schlenk F., Grund S., Fischer D. Recent developments and perspectives on gene therapy using synthetic vectors. Therapeutics Deliv. 2013; 4: 95-113.
  32. Guenther C.M., Kuypers B.E., Lam M.T. et al. Synthetic virology: engineering viruses for gene delivery. WIREs Nanomed. Nanobiotechnol. 2014; 6: 548-58.
  33. Yin H., Kanasty R.L., Eltoukhy A.A. et al. Non-viral vectors for gene-based therapy. Nat. Rev. Genet. 2014; 15: 541-55.
  34. Oliveira C., Silveira I., Veiga F. et al. Recent advances in characterization of nonviral vectors for delivery of nucleic acids: impact on their biological performance. Expert Opin. Drug Deliv. 2015; 12: 27-39.
  35. Fortier C., Durocher Y., De Crescenzo G. Surface modification of nonviral nanocarriers for enhanced gene delivery. Nanomedicine (Lond.) 2014; 9: 135-51.
  36. Hatakeyama H., Akita H., Harashima H. The polyethyleneglycol dilemma: advantage and disadvantage of PEGylation of liposomes for systemic genes and nucleic acids delivery to tumors. Biol. Pharm. Bull. 2013; 36: 892-9.
  37. Wasungu L., Hoekstra D. Cationic lipids, lipoplexes and intracellular delivery of genes. J. Control. Release 2006; 116: 255-64.
  38. Schaffer D.V., Fidelman N.A., Dan N. et al. Vector unpacking as a potential barrier for receptor-mediated polyplex gene delivery. Biotechnol. Bioeng. 2000; 67: 598-606.
  39. Cohen R.N., van der Aa M.A., Macaraeg N. et al. Quantification of plasmid DNA copies in the nucleus after lipoplex and polyplex transfection. J. Control. Release 2009; 135: 166-74.
  40. Yao J., Fan Y., Li al. Strategies on the nuclear-targeted delivery of genes. J. Drug Target. 2013; 21: 926-39.
  41. Mintzer M.A., Simanek E.E. Nonviral vectors for gene delivery. Chem. Rev. 2009; 109: 259-302.
  42. Zhi D., Zhang S., Cui S. et al. The headgroup evolution of cationic lipids for gene delivery. Bioconjug. Chem. 2013; 24: 487-519.
  43. Li W., Szoka F.C. Jr. Lipid-based nanoparticles for nucleic acid delivery. Pharm. Res. 2007; 24: 438-49.
  44. Maslov M.A., Zenkova M.A. Non-viral gene delivery systems based on cholesterol cationic lipids: structure-activity relationships. In: Yuan X., editor. Non-viral gene therapy. Rijeka: InTech; 2011. p. 349-80.
  45. Zhao Y., Huang L. Lipid nanoparticles for gene delivery. Adv. Genet. 2014; 88: 13-36.
  46. Pisani M., Mobbili G., Bruni P. Neutral liposomes and DNA transfection. In: Yuan X., editor. Non-viral gene therapy. Rijeka: InTech; 2011. p. 329-48.
  47. de Jesus M.B., Zuhorn I.S. Solid lipid nanoparticles as nucleic acid delivery system: properties and molecular mechanisms J. Control. Release 2015; 201: 1-13.
  48. Dolatabadi J.E.N., Valizadeh H., Hamishehkar H. Solid lipid nanoparticles as efficient drug and gene delivery systems: recent breakthroughs. Adv. Pharm. Bull. 2015; 5: 151-9.
  49. Su X., Fricke J., Kavanagh D.G. et al. In vitro and in vivo mRNA delivery using lipid-enveloped pH-responsive polymer nanoparticles. Mol. Pharm. 2011; 8: 774-87.
  50. Phua K.K., Leong K.W., Nair S.K. Transfection efficiency and transgene expression kinetics of mRNA delivered in naked and nanoparticle format. J. Control. Release 2013; 166: 227-33.
  51. Akinc A., Querbes W., De S. et al. Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms. Mol. Ther. 2010; 18: 1357-64.
  52. Jayaraman M., Ansell S.M., Mui B.L. et al. Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo. Angew. Chem. Int. Ed. 2012; 51: 8529-33.
  53. Akinc A., Goldberg M., Qin J. et al. Development of lipidoid- siRNA formulations for systemic delivery to the liver. Mol. Ther. 2009; 17: 872-9.
  54. Alabi C.A., Love K.T.; Sahay G. et al. Multiparametric approach for the evaluation of lipid nanoparticles for siRNA delivery. PNAS USA 2013; 110: 12881-6.
  55. Burnett J.C., Rossi J.J., Tiemann K. Current progress of siRNA/shRNA therapeutics in clinical trials. Biotechnol. J. 2011; 6: 1130-46.
  56. Nishina K., Unno T., Uno Y. et al. Efficient in vivo delivery of siRNA to the liver by conjugation of alpha-tocopherol. Mol. Ther. 2008; 16: 734-40.
  57. Petrova N.S., Chernikov I.V., Meschaninova M.I. et al. Carrierfree cellular uptake and the gene-silencing activity of the lipophilic siRNAs is strongly affected by the length of the linker between siRNA and lipophilic group. Nucleic Acids Res. 2012; 40: 2330-44.
  58. Dovydenko I., Tarassov I., Venyaminova A. et al. Method of carrier-free delivery of therapeutic RNA importable into human mitochondria: Lipophilic conjugates with cleavable bonds. Biomaterials 2016; 76: 408-17.
  59. Petrova N.S., Meschaninova M.I., Venyaminova A.G. et al. 2'-O-methyl-modified anti-MDR1 fork-siRNA duplexes exhibiting high nuclease resistance and prolonged silencing activity. Oligonucleotides 2010; 20: 297-308.
  60. Chernolovskaya E.L., Zenkova M.A. Chemical modification of siRNA. Curr. Opin. Mol. Ther. 2010; 12: 158-67.
  61. Aied A., Greiser U., Pandit A. et al. Polymer gene delivery: overcoming the obstacles. Drug Discov. Today 2013; 18: 1090-8.
  62. Neuberg P., Kichler A. Recent developments in nucleic acid delivery with polyethylenimines. Adv. Genet. 2014; 88: 263-88.
  63. Lee Y.S., Kim S.W. Bioreducible polymers for therapeutic gene delivery. J. Control. Release. 2014; 190: 424-39.
  64. Chen W., Meng F., Chenga R. et al. Advanced drug and gene delivery systems based on functional biodegradable polycarbonates and copolymers J. Control. Release 2014; 190: 398-414.
  65. Calejo M.T., Sande S.A., Nyström B. Thermoresponsive polymers as gene and drug delivery vectors: architecture and mechanism of action. Expert Opin. Drug Deliv. 2013; 10: 1669-86.
  66. Cai J., Yue Y., Rui D. et al. Effect of chain length on cytotoxicity and endocytosis of cationic polymers. Macromolecules 2011; 44: 2050-7.
  67. Li L., Wei Y., Gong C. Polymeric nanocarriers for non-viral gene delivery J. Biomed. Nanotechnol. 2015; 11: 739-70.
  68. Nitta S.K., Numata K. Biopolymer-based nanoparticles for drug/gene delivery and tissue engineering. Int. J. Mol. Sci. 2013; 14: 1629-54.
  69. Li Y., Gao G.H., Lee D.S. Stimulus-sensitive polymeric nanoparticles and their applications as drug and gene carriers. Adv. Healthc. Mater. 2013; 2: 388-417.
  70. Draghici B., ilies M.A. Synthetic nucleic acid delivery systems: present and perspectives. J. Med. Chem. 2015; 58: 4091-130.
  71. He D., Wagner E. Defined polymeric materials for gene delivery. Macromol. Biosci. 2015; 15: 600-12.
  72. Liu X., Peng L. Dendrimer nanovectors for siRNA delivery. Methods Mol. Biol. 2016; 1364: 127-42.
  73. Shcharbin D., Shakhbazau A., Bryszewska M. Polytamidoamine) dendrimer complexes as a platform for gene delivery. Expert Opin. Drug Deliv. 2013; 10: 1687-98.
  74. Kesharwani P., iyer A.K. Recent advances in dendrimer-based nanovectors for tumor-targeted drug and gene delivery. Drug Discov. Today 2015; 20: 536-47.
  75. Derossi D., Calvet S., Trembleau A. et al. Cell internalization of the third helix of the Antennapedia homeodomain is receptor-independent. J. Biol. Chem. 1996; 271: 18188-93.
  76. Joliot A., Pernelle C., Deagostini-Bazin H. et al. Antennapedia homeobox peptide regulates neural morphogenesis. PNAS USA 1991: 88: 1864-8.
  77. Vives E., Brodin P., Lebleu B. A truncated HiV-1 TAT protein basic domain rapidly translocates through the plasma membrane and accumulates in the nucleus. J. Biol. Chem. 1997; 272: 16010-7.
  78. Campbell G.R., Loret E.P. What does the structure-function relationship of the HiV-1 Tat protein teach us about developing an AiDS vaccine? Retrovirology 2009; 6: 50.
  79. Gopal V. Bioinspired peptides as versatile nucleic acid delivery platforms. J. Control. Release 2013; 167: 323-32.
  80. Parhiza H., Shierb W.T., Ramezani M. From rationally designed polymeric and peptidic systems to sophisticated gene delivery nano-vectors. int. J. Pharm. 2013; 457: 237-59.
  81. Park J., Singha K., Son S. et al. A review of RGD-functionalized nonviral gene delivery vectors for cancer therapy. Cancer Gene Ther. 2012; 19: 741-8.
  82. Alhakamy N.A., Nigatu A.S., Berkland C.J. et al. Noncovalently associated cell-penetrating peptides for gene delivery applications. Ther. Deliv. 2013; 4: 741-57.
  83. Chou L.Y., Ming K., Chan W.C. Strategies for the intracellular delivery of nanoparticles. Chem. Soc. Rev. 2011; 40: 233-45.
  84. Loh X.J., Lee T.C. Gene delivery by functional inorganic nanocarriers. Recent Pat. DNA Gene Seq. 2012; 6: 108-14.
  85. Loh X.J., Lee T.C., Dou Q. et al. Utilising inorganic nanocarriers for gene delivery. Biomater. Sci. 2016; 4: 70-86.
  86. Ding Y., Jiang Z., Saha K. et al. Gold nanoparticles for nucleic acid delivery. Mol. Ther. 2014; 22: 1075-83.
  87. Jeong E.H., Jung G., Hong C.A. et al. Gold nanoparticle (AuNP)-based drug delivery and molecular imaging for biomedical applications. Arch. Pharm. Res. 2014; 37: 53-9.
  88. Karimi M., Solati N., Amiri M. et al. Carbon nanotubes part i: preparation of a novel and versatile drug-delivery vehicle. Expert Opin. Drug Deliv. 2015; 12: 1071-87.
  89. Karimi M., Solati N., Ghasemi A. et al. Carbon nanotubes part ii: a remarkable carrier for drug and gene delivery. Expert Opin. Drug Deliv. 2015; 12: 1089-105.
  90. Bates K., Kostarelos K. Carbon nanotubes as vectors for gene therapy: past achievements, present challenges and future goals. Adv. Drug Deliv. Rev. 2013; 65: 2023-33.
  91. Bao G., Mitragotri S., Tong S. Multifunctional nanoparticles for drug delivery and molecular imaging. Annu. Rev. Biomed. Eng. 2013; 15: 253-82.
  92. Petkar K.C., Chavhan S.S., Agatonovik-Kustrin S. et al. Nanostructured materials in drug and gene delivery: a review of the state of the art. Crit. Rev. Ther. Drug Carrier Syst. 2011; 28: 101-64.
  93. Wang Y., Huang L. Composite nanoparticles for gene delivery. Adv. Genet. 2014; 88: 111-37.
  94. Wu X., Wu M., Zhao J.X. Recent development of silica nanoparticles as delivery vectors for cancer imaging and therapy. Nanomedicine 2014; 10: 297-312.
  95. Ramamoorth M., Narvekar A. Non-viral vectors in gene therapy - an overview. J. Clin. Diag. Res. 2015; 9(1): GE01-GE06
  96. Zhang D., Das D.B., Rielly C.D. Potential of microneedle-assisted micro-particle delivery by gene guns: a review. Drug Deliv. 2014; 21: 571-87.
  97. Al-Dosari M.S., Gao X. Non-viral gene delivery: principle, limitations and recent progress. AAPS J. 2009; 11: 671-81.
  98. Li S.D., Huang S.L. Gene therapy progress and prospects; Decade strategy. Gene Ther. 2006; 13: 1313-9.
  99. Dean D.A. Cell-specific targeting strategies for electroporation-mediated gene delivery in cells and animals. J. Membrane Biol. 2013; 246: 737-44.
  100. Su C.H., Wu Y.J., Wang H.H. et al. Non-viral gene therapy targeting cardiovascular system. Am. J. Physiol. Heart Circ. Physiol. 2012; 303: H629-38.
  101. Shirley S., Heller R., Heller L. Electroporation gene therapy. in: Lattime E.C., Gerson S.L., editors. Gene therapy of cancer. 3rd ed. San Diego: Academic Press; 2013. p. 93-106.
  102. Zhou Q.L., Chen Z.Y., Wang Y.X. et al. Ultrasound-mediated local drug and gene delivery using nanocarriers. BioMed Res. int. 2014; 2014: 963891.
  103. Cavalli R., Bisazza A., Lembo D. Micro- and nanobubbles: a versatile non-viral platform for gene delivery. int. J. Pharm. 2013; 456: 437-45.
  104. Fan Z., Kumon R.E., Deng C.X. Mechanisms of microbubble-facilitated sonoporation for drug and gene delivery. Ther. Deliv. 2014; 5: 467-86.
  105. Newman C.M., Bettinger T. Gene therapy progress and prospects: Ultrasound for gene transfer. Gene Ther. 2007; 14: 465-75.
  106. Rychak J.J., Klibanov A.L. Nucleic acid delivery with microbubbles and ultrasound. Adv. Drug Deliv. Rev. 2014; 72: 82-93.
  107. Herweiger H., Wolff J.A. Progress and prospects: hydrodynamic gene delivery. Gene Ther. 2006; 14: 99-107.
  108. Ramadori G., Moriconi F., Malik i. et al. Physiology and pathophysiology of liver inflammation, damage and repair. J. Physiol. Pharmacol. 2008; 59 Suppl 1: 107-17.
  109. Salazar-Montes A.M., Hernandez-Ortega L.D., Lucano-Landeros M.S. et al. New gene therapy strategies for hepatic fibrosis. World J. Gastroenterol. 2015; 21: 3813-25.
  110. Nakamuta M., Morizono S., Tsuruta S. et al. Remote delivery and expression of soluble type ii TGF-beta receptor in muscle prevents hepatic fibrosis in rats. int. J. Mol. Med. 2005; 16: 59-64.
  111. Marquez-Aguirre A., Sandoval-Rodriguez A., Gonzalez-Cuevas J. et al. Gene therapy for cirrhosis dominant-negative transforming growth factor beta type ii receptor up-regulates transcriptional repressor SKi-like oncogene, decreases matrix metalloproteinase 2 in hepatic stellate cell and prevents liver fibrosis in rats. J. Gene Med. 2009; 11: 207-19.
  112. Reetz J., Genz B., Meier C. et al. Development of adenoviral delivery systems to target hepatic stellate cells in vivo. PLoS One 2013; 8: e67091.
  113. Liu J., Cheng X., Guo Z. et al. Truncated active human matrix metalloproteinase-8 delivered by a chimeric adenovirus-hepatitis B virus vector ameliorates rat liver cirrhosis. PLoS One 2013; 8: e53392.
  114. Abdul-Wahab A., Qasim W., McGrath J.A. Gene therapies for inherited skin disorders. Semin. Cutan. Med. Surg. 2014; 33: 83-90.
  115. Mavilio F., Pellegrini G., Ferrari S. et al. Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells. Nat. Med. 2006; 12: 1397-402.
  116. Carulli S., Contin R., De Rosa L. et al. The long and winding road that leads to a cure for epidermolysis bullosa. Regen. Med. 2013; 8: 467-81.
  117. Di Nunzio F., Maruggi G., Ferrari S. et al. Correction of laminin-5 deficiency in human epidermal stem cells by transcriptionally targeted lentiviral vectors. Mol. Ther. 2008; 16: 1977-85.
  118. Freiberg R.A., Choate K.A., Deng H. et al. A model of corrective gene transfer in X-linked ichthyosis. Hum. Mol. Genet. 1997; 6: 927-33.
  119. Sawamura D., ina S., itai K. et al. in vivo gene introduction into keratinocytes using jet injection. Gene Ther. 1999; 6: 1785-7.
  120. Sun W.H., Burkholder J.K., Sun J. et al. in vivo cytokine gene transfer by gene gun reduces tumor growth in mice. PNAS USA 1995; 92: 2889-93.
  121. Alexander M.Y., Akhurst R.J. Liposome-medicated gene transfer and expression via the skin. Hum. Mol. Genet. 1995; 4: 2279-85.
  122. Ortiz-Urda S., Thyagarajan B., Keene D.R. et al. Stable nonviral genetic correction of inherited human skin disease. Nat. Med. 2002; 8: 1166-70.
  123. Leachman S.A., Hickerson R.P., Schwartz M.E. et al. First-in-human mutation-targeted siRNA phase ib trial of an inherited skin disorder. Mol.Ther. 2010; 18: 442-6.
  124. McCrudden C.M., McCarthy H.O. Current status of gene therapy for breast cancer: progress and challenges. Appl. Clin. Genet. 2014; 7: 209-20.
  125. Kan O., Griffiths L., Baban D. et al. Direct retroviral delivery of human cytochrome P450 2B6 for gene-directed enzyme prodrug therapy of cancer. Cancer Gene Ther. 2001; 8: 473-82.
  126. Braybrooke J.P., Slade A., Deplanque G. et al. Phase I study of MetXia-P450 gene therapy and oral cyclophosphamide for patients with advanced breast cancer or melanoma. Clin. Cancer Res. 2005; 11: 1512-20.
  127. Gordon E.M., Hall F.L. Noteworthy clinical case studies in cancer gene therapy: tumor-targeted Rexin-G advances as an efficacious anti-cancer agent. Int. J. 0ncol. 2010; 36: 1341-53.
  128. Hu J.C., Coffin R.S., Davis C.J. et al. A phase I study of 0ncoVEXGM-CSF, a second-generation oncolytic herpes simplex virus expressing granulocyte macrophage colony-stimulating factor. Clin. Cancer Res. 2006; 12: 6737-47.
  129. Enderlin M., Kleinmann E.V., Struyf S. et al. TNF-alpha and the IFN-gamma-inducible protein 10 (IP-10/CXCL-10) delivered by parvoviral vectors act in synergy to induce antitumor effects in mouse glioblastoma. Cancer Gene Ther. 2009; 16: 149-60.
  130. Walther W., Siegel R., Kobelt D. et al. Novel jet-injection technology for nonviral intratumoral gene transfer in patients with melanoma and breast cancer. Clin. Cancer Res. 2008; 14: 7545-53.
  131. Shibata M.A., Ito Y., Morimoto J. et al. In vivo electrogene transfer of interleukin-12 inhibits tumor growth and lymph node and lung metastases in mouse mammary carcinomas. J. Gene Med. 2006; 8: 335-52.
  132. Yoo G.H., Hung M.C., Lopez-Berestein G. et al. Phase I trial of intratumoral liposome E1A gene therapy in patients with recurrent breast and head and neck cancer. Clin. Cancer Res. 2001; 7: 1237-45.
  133. Hortobagyi G.N., Ueno N.T., Xia W. et al. Cationic liposome-mediated E1A gene transfer to human breast and ovarian cancer cells and its biologic effects: a phase I clinical trial. J. Clin. 0ncol. 2001; 19: 3422-33.
  134. Gribben J.G., Ryan D.P., Boyajian R. et al. Unexpected association between induction of immunity to the universal tumor antigen CYP1B1 and response to next therapy. Clin. Cancer Res. 2005; 11: 4430-6.
  135. Pandha H.S., Martin L.A., Rigg A. et al. Genetic prodrug activation therapy for breast cancer: a phase I clinical trial of erbB-2-directed suicide gene expression. J. Clin. 0ncol. 1999; 17: 2180-9.
  136. Gao Y., Chen L., Zhang Z. et al. Reversal of multidrug resistance by reduction-sensitive linear cationic click polymer/iMDR1-pDNA complex nanoparticles. Biomaterials 2011; 32: 1738-47.
  137. Feng Q., Yu M.Z., Wang J.C. et al. Synergistic inhibition of breast cancer by co-delivery of VEGF siRNA and paclitaxel via vapreotide-modified core-shell nanoparticles. Biomaterials 2014; 35: 5028-38.
  138. Grosenbaugh D.A., Leard A.T., Bergman P.J. et al. Safety and efficacy of a xenogeneic DNA vaccine encoding for human tyrosinase as adjunctive treatment for oral malignant melanoma in dogs following surgical excision of the primary tumor. Am. J. Vet. Res. 2011; 72: 1631-8.
  139. Bednarek A.K., Sahin A., Brenner A.J. et al. Analysis of telomerase activity levels in breast cancer: positive detection at the in situ breast carcinoma stage. Clin. Cancer Res. 1997; 3: 11-6.
  140. Slamon D., Eiermann W., Robert N. et al. Adjuvant trastuzumab in HER2-positive breast cancer. N. Engl. J. Med. 2011; 365: 1273-83.

Copyright (c) 2016 Eco-Vector

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: ПИ № ФС 77 - 85657 от 21.07.2023 от 11.03.2014.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies