Генная терапия сахарного диабета 2-го типа: состояние и перспективы
DOI: 10.26442/00403660.2019.02.000042
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Stafeev Yu.S., Menshikov M.Yu., Parfyonova Ye.V. Gene therapy of type 2 diabetes mellitus: state of art. Therapeutic Archive. 2019; 91 (2): 8–152. DOI: 10.26442/00403660.2019.02.000042
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Ключевые слова: сахарный диабет 2-го типа, генная терапия, инсулинорезистентность.
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Type 2 diabetes mellitus (T2DM) and other metabolic diseases are essential links in the structure of morbidity and mortality in the modern world. The accepted strategy for the correction of T2DM and insulin resistance is drug therapy aimed at delivering insulin from the outside, stimulating the secretion of own insulin and reducing the concentration of blood glucose. However, modern studies demonstrate a great potential for the use of gene therapy approaches for the correction of T2DM and insulin resistance. In the present review, the main variants of plasmid gene therapy of T2DM using the genes of adiponectin and type 1 glucagon-like peptide, as well as the main variants of viral gene therapy of T2DM using the genes of type 1 and leptin are considered. T2DM gene therapy is currently not ready to enter into routine clinical practice, but, subject to improvements in delivery systems, it can be a powerful link in combination therapy for diabetes.
Keywords: diabetes mellitus type 2, gene therapy, insulin resistance.
2. Herzog RW, Cao O, Srivastava A. Two decades of clinical gene therapy – success is finally mounting. Discov Med. 2010;9:105-11.
3. Couzin-Frankel J. Breakthrough of the year 2013. Cancer immunotherapy. Science. 2013;342:1432-3. doi: 10.1126/science.342.6165.1432
4. Williams PD, Kingston PA. Plasmid-mediated gene therapy for cardiovascular disease. Cardiovasc Res. 2011;91:565-76. doi: 10.1093/cvr/cvr197
5. Laitinen M, Pakkanen T, Donetti E, Baetta R, Luoma J, Lehtolainen P, Viita H, Agrawal R, Miyanohara A, Friedmann T, Risau W, Martin JF, Soma M, Ylä-Herttuala S. Gene transfer into the carotid artery using an adventitial collar: comparison of the effectiveness of the plasmid-liposome complexes, retroviruses, pseudotyped retroviruses, and adenoviruses. Hum Gene Ther. 1997;8:1645-50. doi: 10.1089/hum.1997.8.14-1645
6. Edwards CM. GLP-1: target for a new class of antidiabetic agents? J R Soc Med. 2004;97:270-4.
7. Herzberg-Schäfer S, Heni M, Stefan N, Häring HU, Fritsche A. Impairment of GLP1-induced insulin secretion: role of genetic background, insulin resistance and hyperglycaemia. Diabetes Obes Metab. 2012;14:85-90. doi: 10.1111/j.1463-1326.2012.01648.x
8. Domínguez Avila JA, Rodrigo García J, González Aguilar GA, de la Rosa LA. The antidiabetic mechanisms of polyphenols related to increased glucagon-like peptide-1 (GLP1) and insulin signaling. Molecules. 2017;22:E933. doi: 10.3390/molecules22060903
9. Iwaki M, Matsuda M, Maeda N, Funahashi T, Matsuzawa Y, Makishima M, Shimomura I. Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors. Diabetes. 2003;52:1655-63. doi: 10.2337/diabetes.52.7.1655
10. Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest. 2006;116:1784-92. doi: 10.1172/JCI29126
11. Fisman EZ, Tenenbaum A. Adiponectin: a manifold therapeutic target for metabolic syndrome, diabetes, and coronary disease? Cardiovasc Diabetol. 2014;13:103. doi: 10.1186/1475-2840-13-103
12. Choi S, Oh S, Lee M, Kim SW. Glucagon-like peptide-1 plasmid construction and delivery for the treatment of type 2 diabetes. Mol Ther. 2005;12:885-91. doi: 10.1016/j.ymthe.2005.03.039
13. Parsons GB, Souza DW, Wu H, Yu D, Wadsworth SG, Gregory RJ, Armentano D. Ectopic expression of glucagon-like peptide 1 for gene therapy of type II diabetes. Gene Ther. 2007;14:38-48. doi: 10.1038/sj.gt.3302842
14. Jean M, Alameh M, Buschmann MD, Merzouki A. Effective and safe gene-based delivery of GLP-1 using chitosan/plasmid-DNA therapeutic nanocomplexes in an animal model of type 2 diabetes. Gene Ther. 2011;18:807-16. doi: 10.1038/gt.2011.25
15. Vilsboll T. Liraglutide: a new treatment for type 2 diabetes. Drugs Today (Barc.). 2009;45:101-13. doi: 10.1358/dot.2009.45.2.1336104
16. Verges B, Bonnard C, Renard E. Beyond glucose lowering: glucagon-like peptide-1 receptor agonists, body weight and the cardiovascular system. Diabetes Metab. 2011;37:477-88. doi: 10.1016/j.diabet.2011.07.001
17. Garber AJ. Liraglutide in oral antidiabetic drug combination therapy. Diabetes Obes Metab. 2012;14:13-9. doi: 10.1111/j.1463-1326.2012.01574.x
18. Kim PH, Lee V, Nam K, Kim SW. Enhanced incretin effects of exendin-4 expressing chimeric plasmid based on two-step transcription amplification system with dendritic bioreducible polymer for the treatment of type 2 diabetes. J Gene Ther. 2013;1:7-15. doi: 10.13188/2381-3326.1000002
19. Park JH, Lee M, Kim SW. Non-viral adiponectin gene therapy into obese type 2 diabetic mice ameliorates insulin resistance. J Control Release. 2006;114:118-25. doi: 10.1016/j.jconrel.2006.05.008
20. Nan MH, Park JS, Myung CS. Construction of adiponectin-encoding plasmid DNA and gene therapy of non-obese type 2 diabetes mellitus. J Drug Target. 2010;18:67-77. doi: 10.3109/10611860903225719
21. Kandasamy AD, Sung MM, Boisvenue JJ, Barr AJ, Dyck JR. Adiponectin gene therapy ameliorates high-fat, high-sucrose diet-induced metabolic perturbations in mice. Nutr Diabetes. 2012;2:e45. doi: 10.1038/nutd.2012.18
22. Halenova T, Savchuk O, Ostapchenko L, Chursov A, Fridlyand N, Komissarov A, Venanzi F, Kolesnikov I, Sufianov A, Sherman M, Gabai L, Shneider A. P62 plasmid can alleviate diet-induced obesity and metabolic dysfunctions. Oncotarget. 2017;8:56030-40. doi: 10.18632/oncotarget.19840
23. Jimenez V, Muñoz S, Casana E, Mallol C, Elias I, Jambrina C, Ribera A, Ferre T, Franckhauser S, Bosch F. In vivo adeno-associated viral vector-mediated genetic engineering of white and brown adipose tissue in adult mice. Diabetes. 2013;62:4012-22. doi: 10.2337/db13-0311
24. O'Neill SM, Hinkle C, Chen SJ, Sandhu A, Hovhannisyan R, Stephan S, Lagor WR, Ahima RS, Johnston JC, Reilly MP. Targeting adipose tissue via systemic gene therapy. Gene Ther. 2014;21:653-61. doi: 10.1038/gt.2014.38
25. Gomez-Banoy N, Lo JC. Genetic manipulation with viral vectors to assess metabolism and adipose tissue function. Meth Mol Biol. 2017;1566:109-24. doi: 10.1007/978-1-4939-6820-6_11
26. Riedel MJ, Gaddy DF, Asadi A, Robbins PD, Kieffer TJ. DsAAV8-mediated expression of glucagon-like peptide-1 in pancreatic beta-cells ameliorates streptozotocin-induced diabetes. Gene Ther. 2010;17:171-80. doi: 10.1038/gt.2009.143
27. Lee Y, Kwon MK, Kang ES, Park YM, Choi SH, Ahn CW, Kim KS, Park CW, Cha BS, Kim SW, Sung JK, Lee EJ, Lee HC. Adenoviral vector-mediated glucagon-like peptide 1 gene therapy improves glucose homeostasis in Zucker diabetic fatty rats. J Gene Med. 2008;10:260-8. doi: 10.1002/jgm.1153
28. Tasyurek HM, Altunbas HA, Balci MK, Griffith TS, Sanlioglu S. Therapeutic potential of lentivirus-mediated glucagon-like peptide-1 gene therapy for diabetes. Hum Gene Ther. 2018;29:802-15. doi: 10.1089/hum.2017.180
29. Kojima S, Asakawa A, Amitani H, Sakoguchi T, Ueno N, Inui A, Kalra SP. Central leptin gene therapy, a substitute for insulin therapy to ameliorate hyperglycemia and hyperphagia, and promote survival in insulin-deficient diabetic mice. Peptides. 2009;30:962-6. doi: 10.1016/j.peptides.2009.01.007
30. Wang Y, Asakawa A, Inui A, Kosai K. Leptin gene therapy in the fight against diabetes. Expert Opin Biol Ther. 2010;10:1405-14. doi: 10.1517/14712598.2010.512286
31. Lee MW, Odegaard JI, Mukundan L, Qiu Y, Molofsky AB, Nussbaum JC, Yun K, Locksley RM, Chawla A. Activated type 2 innate lymphoid cells regulate beige fat biogenesis. Cell. 2015;160:74-87. doi: 10.1016/j.cell.2014.12.011
32. Stafeev IS, Michurina SS, Podkuychenko NV, Vorotnikov AV, Menshikov MY, Parfyonova YeV. Interleukin-4 restores insulin sensitivity in lipid-induced insulin resistant adipocytes. Biochemistry (Mosc). 2018;83:498-506. doi: 10.1134/S0006297918050036
33. Michurina S, Stafeev I, Beloglazova I, Molokotina Y, Shevchenko E, Vorotnikov A, Menshikov M, Parfyonova Ye. Lentiviral transfer of interleukin 4 gene to 3T3-L1 adipocytes prevents development of lipid-induced insulin resistance. Eur Heart J. 2018;39:492. doi: 10.1093/eurheartj/ehy565.P2524
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1. Naldini L. Medicine. A comeback for gene therapy. Science. 2009;326:805-6. doi: 10.1126/science.1181937
2. Herzog RW, Cao O, Srivastava A. Two decades of clinical gene therapy – success is finally mounting. Discov Med. 2010;9:105-11.
3. Couzin-Frankel J. Breakthrough of the year 2013. Cancer immunotherapy. Science. 2013;342:1432-3. doi: 10.1126/science.342.6165.1432
4. Williams PD, Kingston PA. Plasmid-mediated gene therapy for cardiovascular disease. Cardiovasc Res. 2011;91:565-76. doi: 10.1093/cvr/cvr197
5. Laitinen M, Pakkanen T, Donetti E, Baetta R, Luoma J, Lehtolainen P, Viita H, Agrawal R, Miyanohara A, Friedmann T, Risau W, Martin JF, Soma M, Ylä-Herttuala S. Gene transfer into the carotid artery using an adventitial collar: comparison of the effectiveness of the plasmid-liposome complexes, retroviruses, pseudotyped retroviruses, and adenoviruses. Hum Gene Ther. 1997;8:1645-50. doi: 10.1089/hum.1997.8.14-1645
6. Edwards CM. GLP-1: target for a new class of antidiabetic agents? J R Soc Med. 2004;97:270-4.
7. Herzberg-Schäfer S, Heni M, Stefan N, Häring HU, Fritsche A. Impairment of GLP1-induced insulin secretion: role of genetic background, insulin resistance and hyperglycaemia. Diabetes Obes Metab. 2012;14:85-90. doi: 10.1111/j.1463-1326.2012.01648.x
8. Domínguez Avila JA, Rodrigo García J, González Aguilar GA, de la Rosa LA. The antidiabetic mechanisms of polyphenols related to increased glucagon-like peptide-1 (GLP1) and insulin signaling. Molecules. 2017;22:E933. doi: 10.3390/molecules22060903
9. Iwaki M, Matsuda M, Maeda N, Funahashi T, Matsuzawa Y, Makishima M, Shimomura I. Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors. Diabetes. 2003;52:1655-63. doi: 10.2337/diabetes.52.7.1655
10. Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest. 2006;116:1784-92. doi: 10.1172/JCI29126
11. Fisman EZ, Tenenbaum A. Adiponectin: a manifold therapeutic target for metabolic syndrome, diabetes, and coronary disease? Cardiovasc Diabetol. 2014;13:103. doi: 10.1186/1475-2840-13-103
12. Choi S, Oh S, Lee M, Kim SW. Glucagon-like peptide-1 plasmid construction and delivery for the treatment of type 2 diabetes. Mol Ther. 2005;12:885-91. doi: 10.1016/j.ymthe.2005.03.039
13. Parsons GB, Souza DW, Wu H, Yu D, Wadsworth SG, Gregory RJ, Armentano D. Ectopic expression of glucagon-like peptide 1 for gene therapy of type II diabetes. Gene Ther. 2007;14:38-48. doi: 10.1038/sj.gt.3302842
14. Jean M, Alameh M, Buschmann MD, Merzouki A. Effective and safe gene-based delivery of GLP-1 using chitosan/plasmid-DNA therapeutic nanocomplexes in an animal model of type 2 diabetes. Gene Ther. 2011;18:807-16. doi: 10.1038/gt.2011.25
15. Vilsboll T. Liraglutide: a new treatment for type 2 diabetes. Drugs Today (Barc.). 2009;45:101-13. doi: 10.1358/dot.2009.45.2.1336104
16. Verges B, Bonnard C, Renard E. Beyond glucose lowering: glucagon-like peptide-1 receptor agonists, body weight and the cardiovascular system. Diabetes Metab. 2011;37:477-88. doi: 10.1016/j.diabet.2011.07.001
17. Garber AJ. Liraglutide in oral antidiabetic drug combination therapy. Diabetes Obes Metab. 2012;14:13-9. doi: 10.1111/j.1463-1326.2012.01574.x
18. Kim PH, Lee V, Nam K, Kim SW. Enhanced incretin effects of exendin-4 expressing chimeric plasmid based on two-step transcription amplification system with dendritic bioreducible polymer for the treatment of type 2 diabetes. J Gene Ther. 2013;1:7-15. doi: 10.13188/2381-3326.1000002
19. Park JH, Lee M, Kim SW. Non-viral adiponectin gene therapy into obese type 2 diabetic mice ameliorates insulin resistance. J Control Release. 2006;114:118-25. doi: 10.1016/j.jconrel.2006.05.008
20. Nan MH, Park JS, Myung CS. Construction of adiponectin-encoding plasmid DNA and gene therapy of non-obese type 2 diabetes mellitus. J Drug Target. 2010;18:67-77. doi: 10.3109/10611860903225719
21. Kandasamy AD, Sung MM, Boisvenue JJ, Barr AJ, Dyck JR. Adiponectin gene therapy ameliorates high-fat, high-sucrose diet-induced metabolic perturbations in mice. Nutr Diabetes. 2012;2:e45. doi: 10.1038/nutd.2012.18
22. Halenova T, Savchuk O, Ostapchenko L, Chursov A, Fridlyand N, Komissarov A, Venanzi F, Kolesnikov I, Sufianov A, Sherman M, Gabai L, Shneider A. P62 plasmid can alleviate diet-induced obesity and metabolic dysfunctions. Oncotarget. 2017;8:56030-40. doi: 10.18632/oncotarget.19840
23. Jimenez V, Muñoz S, Casana E, Mallol C, Elias I, Jambrina C, Ribera A, Ferre T, Franckhauser S, Bosch F. In vivo adeno-associated viral vector-mediated genetic engineering of white and brown adipose tissue in adult mice. Diabetes. 2013;62:4012-22. doi: 10.2337/db13-0311
24. O'Neill SM, Hinkle C, Chen SJ, Sandhu A, Hovhannisyan R, Stephan S, Lagor WR, Ahima RS, Johnston JC, Reilly MP. Targeting adipose tissue via systemic gene therapy. Gene Ther. 2014;21:653-61. doi: 10.1038/gt.2014.38
25. Gomez-Banoy N, Lo JC. Genetic manipulation with viral vectors to assess metabolism and adipose tissue function. Meth Mol Biol. 2017;1566:109-24. doi: 10.1007/978-1-4939-6820-6_11
26. Riedel MJ, Gaddy DF, Asadi A, Robbins PD, Kieffer TJ. DsAAV8-mediated expression of glucagon-like peptide-1 in pancreatic beta-cells ameliorates streptozotocin-induced diabetes. Gene Ther. 2010;17:171-80. doi: 10.1038/gt.2009.143
27. Lee Y, Kwon MK, Kang ES, Park YM, Choi SH, Ahn CW, Kim KS, Park CW, Cha BS, Kim SW, Sung JK, Lee EJ, Lee HC. Adenoviral vector-mediated glucagon-like peptide 1 gene therapy improves glucose homeostasis in Zucker diabetic fatty rats. J Gene Med. 2008;10:260-8. doi: 10.1002/jgm.1153
28. Tasyurek HM, Altunbas HA, Balci MK, Griffith TS, Sanlioglu S. Therapeutic potential of lentivirus-mediated glucagon-like peptide-1 gene therapy for diabetes. Hum Gene Ther. 2018;29:802-15. doi: 10.1089/hum.2017.180
29. Kojima S, Asakawa A, Amitani H, Sakoguchi T, Ueno N, Inui A, Kalra SP. Central leptin gene therapy, a substitute for insulin therapy to ameliorate hyperglycemia and hyperphagia, and promote survival in insulin-deficient diabetic mice. Peptides. 2009;30:962-6. doi: 10.1016/j.peptides.2009.01.007
30. Wang Y, Asakawa A, Inui A, Kosai K. Leptin gene therapy in the fight against diabetes. Expert Opin Biol Ther. 2010;10:1405-14. doi: 10.1517/14712598.2010.512286
31. Lee MW, Odegaard JI, Mukundan L, Qiu Y, Molofsky AB, Nussbaum JC, Yun K, Locksley RM, Chawla A. Activated type 2 innate lymphoid cells regulate beige fat biogenesis. Cell. 2015;160:74-87. doi: 10.1016/j.cell.2014.12.011
32. Stafeev IS, Michurina SS, Podkuychenko NV, Vorotnikov AV, Menshikov MY, Parfyonova YeV. Interleukin-4 restores insulin sensitivity in lipid-induced insulin resistant adipocytes. Biochemistry (Mosc). 2018;83:498-506. doi: 10.1134/S0006297918050036
33. Michurina S, Stafeev I, Beloglazova I, Molokotina Y, Shevchenko E, Vorotnikov A, Menshikov M, Parfyonova Ye. Lentiviral transfer of interleukin 4 gene to 3T3-L1 adipocytes prevents development of lipid-induced insulin resistance. Eur Heart J. 2018;39:492. doi: 10.1093/eurheartj/ehy565.P2524
1 ФГБУ «Национальный медицинский исследовательский центр кардиологии» Минздрава России, Москва, Россия;
2 ФГБУ ВО «Московский государственный университет им. М.В. Ломоносова», Москва, Россия
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Yu.S. Stafeev1,2, M.Yu. Menshikov1, Ye.V. Parfyonova1,2
1 National Medical Research Centre for Cardiology of the Ministry of Health of the Russian Federation, Moscow, Russia;
2 M.V. Lomonosov Moscow State University, Moscow, Russia