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Progress and prospects: gene therapy for performance and appearance enhancement

Gene Therapy volume 15, pages 329–337 (2008)Cite this article

Abstract

While medical therapies aim at reversing, reducing or eliminating diseases, the goal of enhancements is to improve performance or appearance beyond normal levels. Distinction between the two interventions is not always clear as they often present as a continuum. Gene therapy typically aims at treating or preventing disease, but the technology can theoretically be employed for enhancement. Some of the gene therapy enhancement strategies include improving performance by increasing muscle mass, endurance, memory, and cognition and bettering appearance by controlling weight, height and hair growth. In addition to the technical challenges of making enhancement strategies safe and effective, genetic enhancement presents significant ethical/societal questions that must be addressed.

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References

  1. Miller H . Cat and mouse in regulating genetic ‘enhancement’. Nat Biotechnol 2005; 23: 171–172.

    Article  CAS  Google Scholar 

  2. Wenz P . Engineering genetic injustice. Bioethics 2005; 19: 1–11.

    Article  Google Scholar 

  3. The American Society for Aesthetic Plastic Surgery. 11.5 Million Cosmetic Procedures in 2006. (http://www.surgery.org/press/news-release.php?iid=465) last accessed 1/3/08.

  4. Fuchs M . Gene therapy. An ethical profile of a new medical territory. J Gene Med 2006; 8: 1358–1362.

    Article  Google Scholar 

  5. Haisma HJ, de HO . Gene doping. Int J Sports Med 2006; 27: 257–266.

    Article  CAS  Google Scholar 

  6. Allen DB . Growth hormone therapy for short stature: is the benefit worth the burden? Pediatrics 2006; 118: 343–348.

    Article  Google Scholar 

  7. Kimmelman J . Recent developments in gene transfer: risk and ethics. BMJ 2005; 330: 79–82.

    Article  CAS  Google Scholar 

  8. Chan S, Harris J . The ethics of gene therapy. Curr Opin Mol Ther 2006; 8: 377–383.

    PubMed  Google Scholar 

  9. O'Connor TP, Crystal RG . Genetic medicines: treatment strategies for hereditary disorders. Nat Rev Genet 2006; 7: 261–276.

    Article  CAS  Google Scholar 

  10. Lebherz C, Auricchio A, Maguire AM, Rivera VM, Tang W, Grant RL et al. Long-term inducible gene expression in the eye via adeno-associated virus gene transfer in nonhuman primates. Hum Gene Ther 2005; 16: 178–186.

    Article  CAS  Google Scholar 

  11. Walker MC, Mandell TC, Crawford PC, Simon GG, Cahill KS, Fernandes PJ et al. Expression of erythropoietin in cats treated with a recombinant adeno-associated viral vector. Am J Vet Res 2005; 66: 450–456.

    Article  CAS  Google Scholar 

  12. Rivera VM, Gao GP, Grant RL, Schnell MA, Zoltick PW, Rozamus LW et al. Long-term pharmacologically regulated expression of erythropoietin in primates following AAV-mediated gene transfer. Blood 2005; 105: 1424–1430.

    Article  CAS  Google Scholar 

  13. Voutetakis A, Bossis I, Kok MR, Zhang W, Wang J, Cotrim AP et al. Salivary glands as a potential gene transfer target for gene therapeutics of some monogenetic endocrine disorders. J Endocrinol 2005; 185: 363–372.

    Article  CAS  Google Scholar 

  14. Stieger K, Le MG, Lasne F, Weber M, Deschamps JY, Nivard D et al. Long-term doxycycline-regulated transgene expression in the retina of nonhuman primates following subretinal injection of recombinant AAV vectors. Mol Ther 2006; 13: 967–975.

    Article  CAS  Google Scholar 

  15. Mizukami H, Mimuro J, Ogura T, Okada T, Urabe M, Kume A et al. Adipose tissue as a novel target for in vivo gene transfer by adeno-associated viral vectors. Hum Gene Ther 2006; 17: 921–928.

    Article  CAS  Google Scholar 

  16. Wang J, Voutetakis A, Papa M, Rivera VM, Clackson T, Lodde BM et al. Rapamycin control of transgene expression from a single AAV vector in mouse salivary glands. Gene Therapy 2006; 13: 187–190.

    Article  Google Scholar 

  17. Oh TK, Quan GH, Kim HY, Park F, Kim ST . Correction of anemia in uremic rats by intramuscular injection of lentivirus carrying an erythropoietin gene. Am J Nephrol 2006; 26: 326–334.

    Article  CAS  Google Scholar 

  18. Brzezinski M, Yanay O, Waldron L, Barry SC, Osborne WR . G-CSF-lentivirus administration in rats provided sustained elevated neutrophil counts and subsequent EPO-lentivirus administration increased hematocrits. J Gene Med 2007; 9: 571–578.

    Article  CAS  Google Scholar 

  19. Fattori E, Cappelletti M, Zampaglione I, Mennuni C, Calvaruso F, Arcuri M et al. Gene electro-transfer of an improved erythropoietin plasmid in mice and non-human primates. J Gene Med 2005; 7: 228–236.

    Article  CAS  Google Scholar 

  20. Richard P, Pollard H, Lanctin C, Bello-Roufai M, Desigaux L, Escande D et al. Inducible production of erythropoietin using intramuscular injection of block copolymer/DNA formulation. J Gene Med 2005; 7: 80–86.

    Article  CAS  Google Scholar 

  21. Sebestyen MG, Hegge JO, Noble MA, Lewis DL, Herweijer H, Wolff JA . Progress toward a nonviral gene therapy protocol for the treatment of anemia. Hum Gene Ther 2007; 18: 269–285.

    Article  CAS  Google Scholar 

  22. Brill-Almon E, Stern B, Afik D, Kaye J, Langer N, Bellomo S et al. Ex vivo transduction of human dermal tissue structures for autologous implantation production and delivery of therapeutic proteins. Mol Ther 2005; 12: 274–282.

    Article  CAS  Google Scholar 

  23. Lippin Y, Dranitzki-Elhalel M, Brill-Almon E, Mei-Zahav C, Mizrachi S, Liberman Y et al. Human erythropoietin gene therapy for patients with chronic renal failure. Blood 2005; 106: 2280–2286.

    Article  CAS  Google Scholar 

  24. Orive G, De CM, Ponce S, Hernandez RM, Gascon AR, Bosch M et al. Long-term expression of erythropoietin from myoblasts immobilized in biocompatible and neovascularized microcapsules. Mol Ther 2005; 12: 283–289.

    Article  CAS  Google Scholar 

  25. Eliopoulos N, Gagnon RF, Francois M, Galipeau J . Erythropoietin delivery by genetically engineered bone marrow stromal cells for correction of anemia in mice with chronic renal failure. J Am Soc Nephrol 2006; 17: 1576–1584.

    Article  CAS  Google Scholar 

  26. Schakman O, Gilson H, de Coninck V, Lause P, Verniers J, Havaux X et al. Insulin-like growth factor-I gene transfer by electroporation prevents skeletal muscle atrophy in glucocorticoid-treated rats. Endocrinology 2005; 146: 1789–1797.

    Article  CAS  Google Scholar 

  27. Abmayr S, Gregorevic P, Allen JM, Chamberlain JS . Phenotypic improvement of dystrophic muscles by rAAV/microdystrophin vectors is augmented by Igf1 codelivery. Mol Ther 2005; 12: 441–450.

    Article  CAS  Google Scholar 

  28. Kusano K, Tsutsumi Y, Dean J, Gavin M, Ma H, Silver M et al. Long-term stable expression of human growth hormone by rAAV promotes myocardial protection post-myocardial infarction. J Mol Cell Cardiol 2007; 42: 390–399.

    Article  CAS  Google Scholar 

  29. Acosta J, Carpio Y, Borroto I, Gonzalez O, Estrada MP . Myostatin gene silenced by RNAi show a zebrafish giant phenotype. J Biotechnol 2005; 119: 324–331.

    Article  CAS  Google Scholar 

  30. Bartoli M, Poupiot J, Vulin A, Fougerousse F, Arandel L, Daniele N et al. AAV-mediated delivery of a mutated myostatin propeptide ameliorates calpain 3 but not alpha-sarcoglycan deficiency. Gene Therapy 2007; 14: 733–740.

    Article  CAS  Google Scholar 

  31. Nicholas A, Munhoz CD, Ferguson D, Campbell L, Sapolsky R . Enhancing cognition after stress with gene therapy. J Neurosci 2006; 26: 11637–11643.

    Article  CAS  Google Scholar 

  32. Zhang GR, Wang X, Kong L, Lu XG, Lee B, Liu M et al. Genetic enhancement of visual learning by activation of protein kinase C pathways in small groups of rat cortical neurons. J Neurosci 2005; 25: 8468–8481.

    Article  CAS  Google Scholar 

  33. Boghossian S, Lecklin A, Torto R, Kalra PS, Kalra SP . Suppression of fat deposition for the life time with gene therapy. Peptides 2005; 26: 1512–1519.

    Article  CAS  Google Scholar 

  34. Scarpace PJ, Matheny M, Tumer N, Cheng KY, Zhang Y . Leptin resistance exacerbates diet-induced obesity and is associated with diminished maximal leptin signalling capacity in rats. Diabetologia 2005; 48: 1075–1083.

    Article  CAS  Google Scholar 

  35. Lecklin A, Dube MG, Torto RN, Kalra PS, Kalra SP . Perigestational suppression of weight gain with central leptin gene therapy results in lower weight F1 generation. Peptides 2005; 26: 1176–1187.

    Article  CAS  Google Scholar 

  36. Otukonyong EE, Dube MG, Torto R, Kalra PS, Kalra SP . Central leptin differentially modulates ultradian secretory patterns of insulin, leptin and ghrelin independent of effects on food intake and body weight. Peptides 2005; 26: 2559–2566.

    Article  CAS  Google Scholar 

  37. Ueno N, Inui A, Kalra PS, Kalra SP . Leptin transgene expression in the hypothalamus enforces euglycemia in diabetic, insulin-deficient nonobese Akita mice and leptin-deficient obese ob/ob mice. Peptides 2006; 27: 2332–2342.

    Article  CAS  Google Scholar 

  38. Boghossian S, Dube MG, Torto R, Kalra PS, Kalra SP . Hypothalamic clamp on insulin release by leptin-transgene expression. Peptides 2006; 27: 3245–3254.

    Article  CAS  Google Scholar 

  39. Boghossian S, Lecklin A, Dube MG, Kalra PS, Kalra SP . Increased leptin expression in the dorsal vagal complex suppresses adiposity without affecting energy intake and metabolic hormones. Obesity (Silver Spring) 2006; 14: 1003–1009.

    Article  CAS  Google Scholar 

  40. Torto R, Boghossian S, Dube MG, Kalra PS, Kalra SP . Central leptin gene therapy blocks ovariectomy-induced adiposity. Obesity (Silver Spring) 2006; 14: 1312–1319.

    Article  CAS  Google Scholar 

  41. Boghossian S, Ueno N, Dube MG, Kalra P, Kalra S . Leptin gene transfer in the hypothalamus enhances longevity in adult monogenic mutant mice in the absence of circulating leptin. Neurobiol Aging 2007; 28: 1594–1604.

    Article  CAS  Google Scholar 

  42. Scarpace PJ, Matheny M, Zhang Y, Cheng KY, Tumer N . Leptin antagonist reveals an uncoupling between leptin receptor signal transducer and activator of transcription 3 signaling and metabolic responses with central leptin resistance. J Pharmacol Exp Ther 2007; 320: 706–712.

    Article  CAS  Google Scholar 

  43. Li G, Zhang Y, Wilsey JT, Scarpace PJ . Hypothalamic pro-opiomelanocortin gene delivery ameliorates obesity and glucose intolerance in aged rats. Diabetologia 2005; 48: 2376–2385.

    Article  CAS  Google Scholar 

  44. Li G, Zhang Y, Rodrigues E, Zheng D, Matheny M, Cheng KY et al. Melanocortin activation of nucleus of the solitary tract avoids anorectic tachyphylaxis and induces prolonged weight loss. Am J Physiol Endocrinol Metab 2007; 293: E252–E258.

    Article  CAS  Google Scholar 

  45. Li G, Zhang Y, Cheng KY, Scarpace PJ . Lean rats with hypothalamic pro-opiomelanocortin overexpression exhibit greater diet-induced obesity and impaired central melanocortin responsiveness. Diabetologia 2007; 50: 1490–1499.

    Article  CAS  Google Scholar 

  46. Tumer N, Scarpace PJ, Dogan MD, Broxson CS, Matheny M, Yurek DM et al. Hypothalamic rAAV-mediated GDNF gene delivery ameliorates age-related obesity. Neurobiol Aging 2006; 27: 459–470.

    Article  Google Scholar 

  47. Lou H, Crystal RG, Leopold PL . Enhanced efficacy of cholesterol-minus sonic hedgehog in postnatal skin. Mol Ther 2005; 12: 575–578.

    Article  CAS  Google Scholar 

  48. The World Anti-doping Code. The 2006 Prohibited List. (http://www.wada-ama.org/rtecontent/document/2006_LIST.pdf) last accessed 1/3/08.

  49. Gene Doping. Play True—An Official Publication of the World Anti-Doping Agency, 2005. (http://www.wada-ama.org/rtecontent/document/Play_True_01_2005_en.pdf) last accessed 1/3/08.

  50. Azzazy HM, Mansour MM, Christenson RH . Doping in the recombinant era: strategies and counterstrategies. Clin Biochem 2005; 38: 959–965.

    Article  CAS  Google Scholar 

  51. Lippi G, Franchini M, Salvagno GL, Guidi GC . Biochemistry, physiology, and complications of blood doping: facts and speculation. Crit Rev Clin Lab Sci 2006; 43: 349–391.

    Article  CAS  Google Scholar 

  52. Miah A . Rethinking enhancement in sport. Ann NY Acad Sci 2006; 1093: 301–320.

    Article  Google Scholar 

  53. Trent RJ, Alexander IE . Gene therapy in sport. Br J Sports Med 2006; 40: 4–5.

    Article  CAS  Google Scholar 

  54. Baoutina A, Alexander IE, Rasko JE, Emslie KR . Potential use of gene transfer in athletic performance enhancement. Mol Ther 2007; 15: 1751–1766.

    Article  CAS  Google Scholar 

  55. Diamanti-Kandarakis E, Konstantinopoulos PA, Papailiou J, Kandarakis SA, Andreopoulos A, Sykiotis GP . Erythropoietin abuse and erythropoietin gene doping: detection strategies in the genomic era. Sports Med 2005; 35: 831–840.

    Article  Google Scholar 

  56. Heinicke K, Baum O, Ogunshola OO, Vogel J, Stallmach T, Wolfer DP et al. Excessive erythrocytosis in adult mice overexpressing erythropoietin leads to hepatic, renal, neuronal, and muscular degeneration. Am J Physiol Regul Integr Comp Physiol 2006; 291: R947–R956.

    Article  CAS  Google Scholar 

  57. Yla-Herttuala S, Rissanen TT, Vajanto I, Hartikainen J . Vascular endothelial growth factors: biology and current status of clinical applications in cardiovascular medicine. J Am Coll Cardiol 2007; 49: 1015–1026.

    Article  Google Scholar 

  58. Xie D, Li Y, Reed EA, Odronic SI, Kontos CD, Annex BH . An engineered vascular endothelial growth factor-activating transcription factor induces therapeutic angiogenesis in ApoE knockout mice with hindlimb ischemia. J Vasc Surg 2006; 44: 166–175.

    Article  Google Scholar 

  59. Alton E, Ferrari S, Griesenbach U . Progress and prospects: gene therapy clinical trials (part 1). Gene Therapy 2007; 14: 1439–1447.

    Article  Google Scholar 

  60. Bassel-Duby R, Olson EN . Signaling pathways in skeletal muscle remodeling. Annu Rev Biochem 2006; 75: 19–37.

    Article  CAS  Google Scholar 

  61. Schakman O, Thissen JP . Gene therapy with anabolic growth factors to prevent muscle atrophy. Curr Opin Clin Nutr Metab Care 2006; 9: 207–213.

    Article  CAS  Google Scholar 

  62. Walenkamp MJ, Wit JM . Genetic disorders in the growth hormone—insulin-like growth factor-I axis. Horm Res 2006; 66: 221–230.

    CAS  PubMed  Google Scholar 

  63. Matsakas A, Diel P . The growth factor myostatin, a key regulator in skeletal muscle growth and homeostasis. Int J Sports Med 2005; 26: 83–89.

    Article  CAS  Google Scholar 

  64. Joulia-Ekaza D, Cabello G . Myostatin regulation of muscle development: molecular basis, natural mutations, physiopathological aspects. Exp Cell Res 2006; 312: 2401–2414.

    Article  Google Scholar 

  65. Lee SJ, Reed LA, Davies MV, Girgenrath S, Goad ME, Tomkinson KN et al. Regulation of muscle growth by multiple ligands signaling through activin type II receptors. Proc Natl Acad Sci USA 2005; 102: 18117–18122.

    Article  CAS  Google Scholar 

  66. Grimaldi PA . Regulatory role of peroxisome proliferator-activated receptor delta (PPAR delta) in muscle metabolism. A new target for metabolic syndrome treatment? Biochimie 2005; 87: 5–8.

    Article  CAS  Google Scholar 

  67. Arany Z, Lebrasseur N, Morris C, Smith E, Yang W, Ma Y et al. The transcriptional coactivator PGC-1beta drives the formation of oxidative type IIX fibers in skeletal muscle. Cell Metab 2007; 5: 35–46.

    Article  CAS  Google Scholar 

  68. Hautala AJ, Leon AS, Skinner JS, Rao DC, Bouchard C, Rankinen T . Peroxisome proliferator-activated receptor-delta polymorphisms are associated with physical performance and plasma lipids: the HERITAGE Family Study. Am J Physiol Heart Circ Physiol 2007; 292: H2498–H2505.

    Article  CAS  Google Scholar 

  69. Takeshima Y, Yagi M, Wada H, Ishibashi K, Nishiyama A, Kakumoto M et al. Intravenous infusion of an antisense oligonucleotide results in exon skipping in muscle dystrophin mRNA of Duchenne muscular dystrophy. Pediatr Res 2006; 59: 690–694.

    Article  CAS  Google Scholar 

  70. Daniel JM . Effects of oestrogen on cognition: what have we learned from basic research? J Neuroendocrinol 2006; 18: 787–795.

    Article  CAS  Google Scholar 

  71. Kalra SP, Kalra PS . Gene-transfer technology: a preventive neurotherapy to curb obesity, ameliorate metabolic syndrome and extend life expectancy. Trends Pharmacol Sci 2005; 26: 488–495.

    Article  CAS  Google Scholar 

  72. Lee JM, Howell JD . Tall girls: the social shaping of a medical therapy. Arch Pediatr Adolesc Med 2006; 160: 1035–1039.

    Article  Google Scholar 

  73. Peroni CN, Gout PW, Bartolini P . Animal models for growth hormone gene therapy. Curr Gene Ther 2005; 5: 493–509.

    Article  CAS  Google Scholar 

  74. Vogt A, Mandt N, Lademann J, Schaefer H, Blume-Peytavi U . Follicular targeting—a promising tool in selective dermatotherapy. J Investig Dermatol Symp Proc 2005; 10: 252–255.

    Article  Google Scholar 

  75. Hoffman RM . The hair follicle and its stem cells as drug delivery targets. Expert Opin Drug Deliv 2006; 3: 437–443.

    Article  CAS  Google Scholar 

  76. Sugiyama-Nakagiri Y, Akiyama M, Shimizu H . Hair follicle stem cell-targeted gene transfer and reconstitution system. Gene Therapy 2006; 13: 732–737.

    Article  CAS  Google Scholar 

  77. Alton E, Ferrari S, Griesenbach U . Progress and prospects: gene therapy clinical trials (part 2). Gene Therapy 2007; 14: 1555–1563.

    Article  Google Scholar 

  78. Mavilio F, Pellegrini G, Ferrari S, Di NF, Di IE, Recchia A et al. Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells. Nat Med 2006; 12: 1397–1402.

    Article  CAS  Google Scholar 

  79. Whitehouse PJ, Juengst ET . Antiaging medicine and mild cognitive impairment: practice and policy issues for geriatrics. J Am Geriatr Soc 2005; 53: 1417–1422.

    Article  Google Scholar 

  80. Marshall J . Life extension research: an analysis of contemporary biological theories and ethical issues. Med Health Care Philos 2006; 9: 87–96.

    Article  Google Scholar 

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Acknowledgements

We thank N Mohamed for her help in preparing this paper. These studies were supported, in part, by U01 HL66952; U01 NS047458; P01 HL51746 and the Will Rogers Memorial Fund, Los Angeles, CA.

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  1. Department of Genetic Medicine, Weill Medical College of Cornell University, New York, NY, USA

    M Kiuru & R G Crystal

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Kiuru, M., Crystal, R. Progress and prospects: gene therapy for performance and appearance enhancement. Gene Ther 15, 329–337 (2008). https://doi.org/10.1038/sj.gt.3303100

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