Difference between revisions of "Timeline of gene therapy"

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| 1980 || Field development || {{w|Gene transfer}} mediated by {{w|liposome}}s is first described by Fengler.<ref name="Gene Transfer Technique">{{cite web |title=Gene Transfer Technique |url=https://www.mybiosource.com/learn/gene-transfer-technique/ |website=mybiosource.com |accessdate=25 October 2018}}</ref> ||  
 
| 1980 || Field development || {{w|Gene transfer}} mediated by {{w|liposome}}s is first described by Fengler.<ref name="Gene Transfer Technique">{{cite web |title=Gene Transfer Technique |url=https://www.mybiosource.com/learn/gene-transfer-technique/ |website=mybiosource.com |accessdate=25 October 2018}}</ref> ||  
 
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| 1980 || || "The first attempt at modifying human DNA was performed in 1980 by {{w|Martin Cline}}" "The first attempt, an unsuccessful one, at gene therapy (as well as the first case of medical transfer of foreign genes into humans not counting [[organ transplantation]]) was performed by [[Martin Cline]] on 10 July 1980."<ref>{{cite book | title = Human gene therapy – A background paper | author = U.S. Congress, Office of Technology Assessment | publisher = DIANE Publishing | isbn = 978-1-4289-2371-3 | url = https://books.google.com/?id=FxGjBqEL-3kC&pg=PA45 | date = December 1984 }}</ref><ref>{{cite journal | vauthors = Sun M | title = Martin Cline loses appeal on NIH grant | journal = Science | volume = 218 | issue = 4567 | pages = 37 | date = October 1982 | pmid = 7123214 | doi = 10.1126/science.7123214}}</ref> ||
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| 1980 || Field development || American scientist and physician {{w|Martin Cline}} from the {{w|University of California Los Angeles}} (UCLA), becomes the first investigator to attempt gene therapy using {{w|rDNA}}. Cline administers recombinant DNAwith the hope of effecting gene transfer in two patients with thalassemia, one in {{w|Israel}} and the other in {{w|Italy}}. The attempt fails.<ref>{{cite book | title = Human gene therapy – A background paper | author = U.S. Congress, Office of Technology Assessment | publisher = DIANE Publishing | isbn = 978-1-4289-2371-3 | url = https://books.google.com/?id=FxGjBqEL-3kC&pg=PA45 | date = December 1984 }}</ref><ref>{{cite journal | vauthors = Sun M | title = Martin Cline loses appeal on NIH grant | journal = Science | volume = 218 | issue = 4567 | pages = 37 | date = October 1982 | pmid = 7123214 | doi = 10.1126/science.7123214}}</ref><ref>{{cite book |last1=Kelly |first1=Evelyn B. |title=Gene Therapy |url=https://books.google.com.ar/books?id=4AG1vWp6SjoC&pg=PA33&dq=%22in+1980%22+%22Martin+Cline%22&hl=en&sa=X&ved=0ahUKEwi3wab_w6LeAhWDEpAKHaGuCHYQ6AEIKTAA#v=onepage&q=%22in%201980%22%20%22Martin%20Cline%22&f=false}}</ref><ref>{{cite book |title=Preserving Public Trust: Accreditation and Human Research Participant Protection Programs |publisher=Institute of Medicine, Board on Health Sciences Policy, Committee on Assessing the System for Protecting Human Research Subjects |url=https://books.google.com.ar/books?id=TpucAgAAQBAJ&pg=PT74&dq=%22in+1980%22+%22Martin+Cline%22&hl=en&sa=X&ved=0ahUKEwi3wab_w6LeAhWDEpAKHaGuCHYQ6AEILjAB#v=onepage&q=%22in%201980%22%20%22Martin%20Cline%22&f=false}}</ref><ref>{{cite book |last1=Serafini |first1=Anthony |title=The Epic History of Biology |url=https://books.google.com.ar/books?id=Z3oECAAAQBAJ&pg=PA353&dq=%22in+1980%22+%22Martin+Cline%22&hl=en&sa=X&ved=0ahUKEwi3wab_w6LeAhWDEpAKHaGuCHYQ6AEINjAC#v=onepage&q=%22in%201980%22%20%22Martin%20Cline%22&f=false}}</ref> || {{w|Israel}}, {{w|Italy}}
 
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| 1983 || Field development || A group of scientists from {{w|Baylor College of Medicine}} in {{w|Houston}}, {{w|Texas}}, propose that gene therapy could one day be a viable approach for treating {{w|Lesch-Nyhan disease}}, a rare neurological disorder.<ref name="Gene TherapyGene Therapy">{{cite web |title=Gene Therapy |url=https://www.encyclopedia.com/medicine/divisions-diagnostics-and-procedures/medicine/gene-therapy |website=encyclopedia.com |accessdate=18 October 2018}}</ref> || {{w|United States}}
 
| 1983 || Field development || A group of scientists from {{w|Baylor College of Medicine}} in {{w|Houston}}, {{w|Texas}}, propose that gene therapy could one day be a viable approach for treating {{w|Lesch-Nyhan disease}}, a rare neurological disorder.<ref name="Gene TherapyGene Therapy">{{cite web |title=Gene Therapy |url=https://www.encyclopedia.com/medicine/divisions-diagnostics-and-procedures/medicine/gene-therapy |website=encyclopedia.com |accessdate=18 October 2018}}</ref> || {{w|United States}}

Revision as of 13:33, 25 October 2018

This is a timeline of gene therapy.

Big picture

Time period Development summary
1960s Gene therapy as a concept is first introduced in the 1960s. Scientists are able to incorporate functional DNA inside human cells in vivo as early as 1961.[1]
By the late 1960s and early 1970s, gene therapy becomes the subject of an increasing number of articles and meetings.[2]
1980s As the science of genetics advances throughout the decade, gene therapy gains an established foothold in the minds of medical scientists as a promising approach to treatments for specific diseases.[3]
1990s The decade brings further innovations, such as the first use of hematopoietic stem cells as vectors to deliver corrective genes. However, the death of Jesse Gelsinger in 1999, who dies following a major immune response to a vector used in clinical trial, has a major negative impact on the field of gene therapy.[1]
2010s Gene therapy is introduced in the European market first, and later in the United States.[1]

Full timeline

Year Event type Details Location
1928 British bacteriologist Frederick Griffith describes the transforming principle.[4][5][6] United Kingdom
1944 Oswald Avery, Colin MacLeod, and Maclyn McCarty describe that genetic information is carried in the form of DNA. The team finds that a gene is a part of DNA itself. This experimental demonstration is later called Avery–MacLeod–McCarty experiment.[7][8][9] United States
1952 American molecular biologist Joshua Lederberg introduces transduction as a mechanism of genetic transfer.[10][11][12] United States
1953 American molecular biologist James Watson and British molecular biologist Francis Crick identify the double-stranded structure of the DNA.[13]
1961 American virologist Howard Martin Temin discovers that genetic mutation could be inherited as a result of virus infection.[14]
1961 Scientists first manage to incorporate functional DNA inside human cells in vivo.[1]
1962 The possibility of gene therapy is speculated.[13][2]
1962 Polish professor Wacław Szybalski coins the term gene therapy.[15]
1968 Early attempts at use of viral vectors.[13] Rogers and Pfuderer demonstrate a proof-of-concept for virus mediated gene transfer.[16][17][18]
1969 Aposhian proposes the use of pseudoviruses derived from the mouse virus, polyoma.[2]
1970 Howard Martin Temin and David Baltimore discover reverse transcriptase, an enzyme used to generate complementary DNA (cDNA) from an RNA template.[19][20][21][13]
1971 A symposium on gene therapy is sponsored by the National Institute of Neuologic Disease and Stroke at the NIH and the Fogarty International Center.[2]
1972 Professor Theodore Friedmann and his colleague Richard Roblin, from the University of California, San Diego, discuss gene therapy in an article published in Science.[2] They suggest that transforming viruses could be used for therapeutic gene transfer.[13][22][23][24] United States
1973 Field development Graham and van der Erb introduce calcium phosphate transfection.[13]
1976 Field development A meeting sponsored by the New York Academy of Sciences discusses the new subject of gene therapy.[2] United States
1978 Field development American scientist Paul Zamecnik et al. suggest that oligonucleotides could be used therapeutically.[25][13] United States
1980 Field development Gene transfer mediated by liposomes is first described by Fengler.[26]
1980 Field development American scientist and physician Martin Cline from the University of California Los Angeles (UCLA), becomes the first investigator to attempt gene therapy using rDNA. Cline administers recombinant DNAwith the hope of effecting gene transfer in two patients with thalassemia, one in Israel and the other in Italy. The attempt fails.[27][28][29][30][31] Israel, Italy
1983 Field development A group of scientists from Baylor College of Medicine in Houston, Texas, propose that gene therapy could one day be a viable approach for treating Lesch-Nyhan disease, a rare neurological disorder.[3] United States
1983 Scientists at the Massachussets Institute of Technology create the first retroviral vector suitable for use in gene therapy from a mouse leukemia virus.[1] United States
1984 Experiment shows that targeted insertion of corrective DNA is possible in mammalian cells in vitro.[1]
1984 "(Izant and Weintraub 1984)First demonstration that antisense nucleic acid can be used to downregulate gene expression"[13]
1984 A retrovirus vector system is designed that could efficiently insert foreign genes into mammalian chromosomes.[32]
1987 "(Hoffman et al 1987)Identification of dystrophin, the protein product of Duchenne muscular dystrophy gene (basis of future gene therapy of this disorder)"[13]
1989 The first successful nuclear gene transfer in humans, approved by the United States National Institutes of Health, is conducted by American cancer researcher Steven A. Rosenberg.[33][34][35] United States
1989 Trials for somatic gene therapy are run for various forms of cancer, familial hypercholesterolemia, hemophilia, and even AIDS.[36]
1990 The first gene therapy widely accepted as a success is demonstrated when four-year-old Ashi DeSilva is treated for ADA-SCID.[37] In the trial, Blaese et al manage to correct the adenosine deaminase deficiency in T-lymphocytes using retroviral-mediated gene transfer.[22][22][3] United States
1991 (Hazinski et al 1991)Use of cationic liposome for gene transfer in experimental animals"[22]
1991 Financial The United States Government provides US$58 million for gene therapy research, with increases in funding of US$15-40 million dollars a year over the following four years.[3] United States
1992 Field development Correction of myopathy is carried out in a transgenic mouse model of Duchenne muscular dystrophy by germline gene transfer of human dystrophin using a retroviral vector.[38][13]
1992 Claudio Bordignon, working at the Vita-Salute San Raffaele University, performs the first gene therapy procedure using hematopoietic stem cells as vectors to deliver genes intended to correct hereditary diseases.[39]
1992–1993 Field development Cancer gene therapy is introduced by Trojan et al.[40]
1993 "(Oldfield and Ram 1993)First clinical trial of herpes simplex virus/thymidine kinase/ganciclovir gene therapy system in glioblastoma multiforme"[13]
1993 Experimental trials are run in London on a somatic gene therapy for cystic fibrosis (CF).[36] United Kingdom
1995 "(Aebischer and Kato 1995)Treatment of amyotrophic lateral sclerosis using a gene therapy approach involving implantation of genetically engineered microencapsulated cells releasing neurotrophic factors."[13]
1998 "(Fire et al 1998)RNA interference demonstrated: injection of double stranded RNA shown to inhibit genes."[13]
1999 American patient Jesse Gelsinger dies following a gene therapy experiment, impeding gene therapy research and setting the field back several years as U.S. regulators put some key experiments on hold.[22][41][42] As a result, the U.S. Food and Drug Administration suspends several clinical trials pending the reevaluation of ethical and procedural practices.[43] United States
2000 "(Collins 2000)Completion of sequencing phase of human genome project. Further developments in next-generation sequencing in the following years had considerable impact on personalized medicine. For neurologic disorders, it led to improved diagnostics, identification of gene mutations, and development of therapies targeting these (Yuan et al 2015)."[13]
2002–2003 Cases of leukemia are diagnosed in French children undergoing gene therapy for genetic immunodeficiency.[22][44]
2003 The first commercial gene therapy, Gendicine, is approved in China for the treatment of head and neck cancer.[45][22] China becomes the first country to approve a gene therapy based product for clinical use. China
2005 " Oncorine (Shanghai Sunway Biotech, Shanghai, China). E1B-defective Ad for the treatment of head and neck cancer."[46] China
2006 (March) Researchers announce the successful use of gene therapy to treat two adult patients for X-linked chronic granulomatous disease, a disease which affects myeloid cells and damages the immune system. The study is the first to show that gene therapy can treat the myeloid system.[47]
2006 (May) A team reports a way to prevent the immune system from rejecting a newly delivered gene.[48]
2006 (August) Scientists successfully treat metastatic melanoma in two patients using killer T cells genetically retargeted to attack the cancer cells.[49]
2006 (November) Researchers report on the use of VRX496, a gene-based immunotherapy for the treatment of HIV that uses a lentiviral vector to deliver an antisense gene against the HIV envelope. This is the first evaluation of a lentiviral vector administered in a human clinical trial in the United States.[50][51] United States
2007 (May) Researchers announce the first gene therapy trial for inherited retinal disease. The first operation is carried out on a 23-year-old British male, Robert Johnson, in early 2007.[52]
2007 "2007 - British doctors carry out the world’s first operation using gene therapy to treat a serious sight disorder caused by a genetic defect."[22]
2007–2008 Timothy Ray Brown is cured of HIV by repeated hematopoietic stem cell transplantation.[53] United States
2009 (September) Using gene therapy, researchers manage to give trichromatic vision to squirrel monkeys.[54]
2009 (November) Researchers halt a fatal genetic disorder called adrenoleukodystrophy in two children using a lentivirus vector to deliver a functioning version of ABCD1, the gene that is mutated in the disorder.[55]
2010 "(Garneau et al 2010)Definition of critical components of the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 system, which later formed the basis of gene editing."[13]
2010 (April) A paper reports that gene therapy addresses achromatopsia (color blindness) in dogs by targeting cone photoreceptors. Cone function and day vision are restored for at least 33 months in two young specimens. The therapy is less efficient for older dogs.[56]
2010 (September) Gene therapy successfully treates 18-year-old male patient in France with beta-thalassemia.[57] France
2010–2011 Cancer immunogene therapy using modified antigene, antisense/triple helix approach is introduced in South America in University of La Sabana, Bogota.[58][59] Colombia
2011 Neovasculgen is registered in Russia as the first-in-class gene-therapy drug for treatment of peripheral artery disease, including critical limb ischemia.[60][46]
2012 Glybera, a treatment for a rare inherited disorder, becomes the first treatment to be approved for clinical use in both Europe and the United States after its endorsement by the European Commission.[61][22][62]
2014 "2014 - Gene therapy shows promise in clinical trials for inherited blood disorders, certain types of progressive blindness and HIV."[22]
2017 The United States Food and Drug Administration approves the first gene therapy, tisagenlecleucel (Kymriah), for refractory B-cell precursor acute lymphoblastic leukemia.[63] United States

Meta information on the timeline

How the timeline was built

The initial version of the timeline was written by User:Sebastian.

Funding information for this timeline is available.

Feedback and comments

Feedback for the timeline can be provided at the following places:

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What the timeline is still missing

[1], [2], [3], [4], [5], [6], [7], [8]

Timeline update strategy

See also

External links

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 "Gene Therapy 101: From The 1960s To Today". premier-research.com. Retrieved 18 October 2018. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Wolff, Jon A. Gene Therapeutics: Methods and Applications of Direct Gene Transfer. 
  3. ↑ 3.0 3.1 3.2 3.3 "Gene Therapy". encyclopedia.com. Retrieved 18 October 2018. 
  4. ↑ Renneberg, Reinhard; Berkling, Viola; Loroch, Vanya. Biotechnology for Beginners. 
  5. ↑ Tmh. Target 2011: Biology 12. 
  6. ↑ Chamary, JV. 50 Biology Ideas You Really Need to Know. 
  7. ↑ Ohya, Masanori; Watanabe, Noboru. Selected Papers of M. Ohya. 
  8. ↑ Principles and Applications of Molecular Diagnostics (Nader Rifai, A. Rita Horvath, Carl T. Wittwer, Jason Park ed.). 
  9. ↑ Hoffee, P. A. Medical Molecular Genetics, Volume 698. 
  10. ↑ Biomaterials for Bone Regeneration: Novel Techniques and Applications (P. Dubruel, S. Van Vlierberghe ed.). 
  11. ↑ Maheshwari, D.K. A Textbook of Microbiology. 
  12. ↑ Snyder, Larry; Champness, Wendy. Molecular Genetics of Bacteria. 
  13. ↑ 13.00 13.01 13.02 13.03 13.04 13.05 13.06 13.07 13.08 13.09 13.10 13.11 13.12 13.13 13.14 "Gene therapy". medlink.com. Retrieved 15 October 2018. 
  14. ↑ Biomaterials for Bone Regeneration: Novel Techniques and Applications (P. Dubruel, S. Van Vlierberghe ed.). 
  15. ↑ Twyman, Richard. Gene Transfer to Animal Cells. 
  16. ↑ Prazeres, Duarte Miguel F. Plasmid Biopharmaceuticals: Basics, Applications, and Manufacturing. 
  17. ↑ Gene Therapeutics: Methods and Applications of Direct Gene Transfer (Jon A. Wolff ed.). 
  18. ↑ The Development of Human Gene Therapy (Theodore Friedmann ed.). 
  19. ↑ Varmus, Harold. The Art and Politics of Science. 
  20. ↑ Pennington, T. H. Molecular Virology. 
  21. ↑ Snustad, D. Peter; Simmons, Michael J. Principles of Genetics, Binder Ready Version. 
  22. ↑ 22.0 22.1 22.2 22.3 22.4 22.5 22.6 22.7 22.8 22.9 "TIMELINE-Milestones in gene therapy". reuters.com. Retrieved 15 October 2018. 
  23. ↑ Tramper, J.; Zhu, Yang. Modern Biotechnology: Panacea or new Pandora's box?. 
  24. ↑ Shapiro, Irving M.; Risbud, Makarand V. The Intervertebral Disc: Molecular and Structural Studies of the Disc in Health and Disease. 
  25. ↑ "Zamecnik, P.C. & Stephenson, M.L. Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide. Proc. Natl. Acad. Sci. USA 75, 280-284". researchgate.net. Retrieved 19 October 2018. 
  26. ↑ "Gene Transfer Technique". mybiosource.com. Retrieved 25 October 2018. 
  27. ↑ U.S. Congress, Office of Technology Assessment (December 1984). Human gene therapy – A background paper. DIANE Publishing. ISBN 978-1-4289-2371-3. 
  28. ↑ Sun M (October 1982). "Martin Cline loses appeal on NIH grant". Science. 218 (4567): 37. PMID 7123214. doi:10.1126/science.7123214. 
  29. ↑ Kelly, Evelyn B. Gene Therapy. 
  30. ↑ Preserving Public Trust: Accreditation and Human Research Participant Protection Programs. Institute of Medicine, Board on Health Sciences Policy, Committee on Assessing the System for Protecting Human Research Subjects. 
  31. ↑ Serafini, Anthony. The Epic History of Biology. 
  32. ↑ Cepko CL, Roberts BE, Mulligan RC (July 1984). "Construction and applications of a highly transmissible murine retrovirus shuttle vector". Cell. 37 (3): 1053–62. PMID 6331674. doi:10.1016/0092-8674(84)90440-9. 
  33. ↑ Rosenberg SA, Aebersold P, Cornetta K, Kasid A, Morgan RA, Moen R, et al. (August 1990). "Gene transfer into humans--immunotherapy of patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral gene transduction". The New England Journal of Medicine. 323 (9): 570–8. PMID 2381442. doi:10.1056/NEJM199008303230904. 
  34. ↑ March, Keith L. Gene Transfer in the Cardiovascular System: Experimental Approaches and Therapeutic Implications. 
  35. ↑ Barh, Debmalya; Azevedo, Vasco. Omics Technologies and Bio-engineering: Volume 1: Towards Improving Quality of Life. 
  36. ↑ 36.0 36.1 The Concise Encyclopedia of the Ethics of New Technologies. 
  37. ↑ Sheridan C (February 2011). "Gene therapy finds its niche". Nature Biotechnology. 29 (2): 121–8. PMID 21301435. doi:10.1038/nbt.1769. 
  38. ↑ "Gene therapy of muscular dystrophy". medlink.com. Retrieved 25 October 2018. 
  39. ↑ Abbott A (April 1992). "Gene therapy. Italians first to use stem cells". Nature. 356 (6369): 465. PMID 1560817. doi:10.1038/356465a0. 
  40. ↑ Trojan J, Johnson TR, Rudin SD, Ilan J, Tykocinski ML, Ilan J (January 1993). "Treatment and prevention of rat glioblastoma by immunogenic C6 cells expressing antisense insulin-like growth factor I RNA". Science. 259 (5091): 94–7. Bibcode:1993Sci...259...94T. PMID 8418502. doi:10.1126/science.8418502. 
  41. ↑ Stein R (11 October 2010). "First patient treated in stem cell study". The Washington Post. Retrieved 17 October 2018. 
  42. ↑ "Death Prompts FDA to Suspend Arthritis Gene Therapy Trial". Medpage Today. 27 July 2007. Retrieved 17 October 2018. 
  43. ↑ Stolberg SG (22 January 2000). "Gene Therapy Ordered Halted At University". The New York Times. Retrieved 17 October 2018. 
  44. ↑ "somatic gene therapy". unifr.ch. Retrieved 19 October 2018. 
  45. ↑ Pearson S, Jia H, Kandachi K (January 2004). "China approves first gene therapy". Nature Biotechnology. 22 (1): 3–4. PMID 14704685. doi:10.1038/nbt0104-3. 
  46. ↑ 46.0 46.1 "The history of gene therapy drugs approval on the market". stemcellassays.com. Retrieved 18 October 2018. 
  47. ↑ Ott MG, Schmidt M, Schwarzwaelder K, Stein S, Siler U, Koehl U, et al. (April 2006). "Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1". Nature Medicine. 12 (4): 401–9. PMID 16582916. doi:10.1038/nm1393. 
  48. ↑ Brown BD, Venneri MA, Zingale A, Sergi Sergi L, Naldini L (May 2006). "Endogenous microRNA regulation suppresses transgene expression in hematopoietic lineages and enables stable gene transfer". Nature Medicine. 12 (5): 585–91. PMID 16633348. doi:10.1038/nm1398. 
  49. ↑ Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, et al. (October 2006). "Cancer regression in patients after transfer of genetically engineered lymphocytes". Science. 314 (5796): 126–9. Bibcode:2006Sci...314..126M. PMC 2267026Freely accessible. PMID 16946036. doi:10.1126/science.1129003. 
  50. ↑ Levine BL, Humeau LM, Boyer J, MacGregor RR, Rebello T, Lu X, et al. (November 2006). "Gene transfer in humans using a conditionally replicating lentiviral vector". Proceedings of the National Academy of Sciences of the United States of America. 103 (46): 17372–7. Bibcode:2006PNAS..10317372L. PMC 1635018Freely accessible. PMID 17090675. doi:10.1073/pnas.0608138103. 
  51. ↑ "Penn Medicine presents HIV gene therapy trial data at CROI 2009". EurekAlert!. 10 February 2009. Retrieved 17 October 2018. 
  52. ↑ "Gene therapy first for poor sight". BBC News. 1 May 2007. Retrieved 17 October 2018. 
  53. ↑ Rosenberg, Tina (29 May 2011) The Man Who Had HIV and Now Does Not, New York.
  54. ↑ Dolgin E (2009). "Colour blindness corrected by gene therapy". Nature. doi:10.1038/news.2009.921. 
  55. ↑ Cartier N, Hacein-Bey-Abina S, Bartholomae CC, Veres G, Schmidt M, Kutschera I, et al. (November 2009). "Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy". Science. 326 (5954): 818–23. Bibcode:2009Sci...326..818C. PMID 19892975. doi:10.1126/science.1171242. 
  56. ↑ Komáromy AM, Alexander JJ, Rowlan JS, Garcia MM, Chiodo VA, Kaya A, et al. (July 2010). "Gene therapy rescues cone function in congenital achromatopsia". Human Molecular Genetics. 19 (13): 2581–93. PMC 2883338Freely accessible. PMID 20378608. doi:10.1093/hmg/ddq136. 
  57. ↑ Cavazzana-Calvo M, Payen E, Negre O, Wang G, Hehir K, Fusil F, et al. (September 2010). "Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia". Nature. 467 (7313): 318–22. Bibcode:2010Natur.467..318C. PMC 3355472Freely accessible. PMID 20844535. doi:10.1038/nature09328. 
  58. ↑ Trojan An Aristizabal B, Jay LM, Castillo T, Penagos P, Trojan J. Testing of IGF-I biomarker in an ethical context. Adv Modern Oncol Res, 2(4); 2016, Template:Doi
  59. ↑ Castillo T, Trojan A, Noguera MC, Jay ML, Crane C, Alvarez A, Melo G, Penagos PJ, Shevelev A, Aristizabal BH, Briceño I, Ayala A, Duc HT, Trojan J. Epidemiologic experience in elaboration of molecular biology technology for immunogene therapy (in Spanish). Rev Cien, 2 (25); 2016, Template:Doi
  60. ↑ "Gene Therapy for PAD Approved". 6 December 2011. Retrieved 17 October 2018. 
  61. ↑ Richards S (6 November 2012). "Gene Therapy Arrives in Europe". The Scientist. 
  62. ↑ Gallagher, James. (2 November 2012) BBC News – Gene therapy: Glybera approved by European Commission. BBC. Retrieved 15 December 2012.
  63. ↑ "The Past and Future of Gene Therapy". specialtypharmacytimes.com. Retrieved 18 October 2018. 
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