Timeline of gene therapy

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This is a timeline of gene therapy, attempting to describe significant events in the development of the field.

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 Field development British bacteriologist Frederick Griffith describes the transforming principle.[4][5][6] United Kingdom
1944 Field development 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 Field development American molecular biologist Joshua Lederberg introduces transduction as a mechanism of genetic transfer.[10][11][12] United States
1953 Field development American molecular biologist James Watson and British molecular biologist Francis Crick identify the double-stranded structure of the DNA.[13]
1961 Field development American virologist Howard Martin Temin discovers that genetic mutation could be inherited as a result of virus infection.[14]
1961 Field development Scientists first manage to incorporate functional DNA inside human cells in vivo.[1]
1962 Field development The possibility of gene therapy is speculated.[13][2]
1962 Field development Polish professor Wacław Szybalski coins the term gene therapy.[15]
1968 Application 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 Application Aposhian proposes the use of pseudoviruses derived from the mouse virus, polyoma.[2]
1970 Field development 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 Field development 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 Field development 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 Field development Experiment shows that targeted insertion of corrective DNA is possible in mammalian cells in vitro.[1]
1984 Field development Izant and Weintraub first demonstrate that antisense nucleic acid can be used to downregulate gene expression.[13]
1984 Field development A retrovirus vector system is designed that could efficiently insert foreign genes into mammalian chromosomes.[32]
1987 Field development Hoffman et al identify dystrophin, the protein product of Duchenne muscular dystrophy gene (basis of future gene therapy of this disorder).[13]
1988 Literature Eve K. Nichols publishes Human Gene Therapy.[33] United States
1989 Field development 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.[34][35][36] United States
1989 Application Trials for somatic gene therapy are run for various forms of cancer, familial hypercholesterolemia, hemophilia, and even AIDS.[37]
1990 Application The first gene therapy widely accepted as a success is demonstrated when four-year-old Ashi DeSilva is treated for ADA-SCID.[38] 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 Field development Hazinski et al make 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.[39][13]
1992 Application 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.[40]
1992–1993 Application Cancer gene therapy is introduced by Trojan et al.[41]
1993 Application Oldfield and Ram conduct the first clinical trial of herpes simplex virus/thymidine kinase/ganciclovir gene therapy system in glioblastoma multiforme.[13]
1993 Application Experimental trials are run in London on a somatic gene therapy for cystic fibrosis (CF).[37] United Kingdom
1995 Application Aebischer and Kato manage to treat amyotrophic lateral sclerosis using a gene therapy approach involving implantation of genetically engineered microencapsulated cells releasing neurotrophic factors.[13]
1996 Organization The American Society of Gene and Cell Therapy (ASGCT) is established.[42] United States
1998 Field development Fire et al demonstrate RNA interference: injection of double stranded RNA shown to inhibit genes.[13]
1999 Notable death 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][43][44] As a result, the U.S. Food and Drug Administration suspends several clinical trials pending the reevaluation of ethical and procedural practices.[45] United States
1999 Literature Edmund C. Lattime and Stanton L. Gerson publish Gene Therapy of Cancer: Translational Approaches from Preclinical Studies to Clinical Implementation.[46]
2000 Field development American physician-geneticist Francis Collins completes the sequencing phase of the human genome project. Further developments in next-generation sequencing in the following years would have considerable impact on personalized medicine. For neurological disorders, it would lead to improved diagnostics, identification of gene mutations, and development of therapies targeting these.[13]
2002 Literature David T. Curiel and Joanne T. Douglas publish Adenoviral Vectors for Gene Therapy.[47]
2002–2003 Cases of leukemia are diagnosed in French children undergoing gene therapy for genetic immunodeficiency.[22][48]
2003 Drug The first commercial gene therapy, Gendicine, is approved in China for the treatment of head and neck cancer.[49][22] China becomes the first country to approve a gene therapy based product for clinical use. China
2004 Literature David T. Curiel and Joanne T. Douglas publish Cancer Gene Therapy.[50]
2005 Drug The China Food and Drug Administration approves its first oncolytic adenovirus drug Oncorine (H101), for treatment of advanced head and neck cancer.[51] Adenovirus varieties have been explored extensively as a viral vector for gene therapy and also as an oncolytic virus.[52][53] China
2006 (March) Application 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.[54]
2006 (May) Field development A team reports a way to prevent the immune system from rejecting a newly delivered gene.[55]
2006 (August) Application Scientists successfully treat metastatic melanoma in two patients using killer T cells genetically retargeted to attack the cancer cells.[56]
2006 (November) Application 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.[57][58] United States
2007 (May) Application 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.[59]
2007 Application Doctors in Great Britain conduct the world’s first operation using gene therapy to treat a serious sight disorder caused by a genetic defect.[22] United Kingdom
2007–2008 Application Timothy Ray Brown is cured of HIV by repeated hematopoietic stem cell transplantation.[60] United States
2008 Literature Roland W. Herzog publishes Gene Therapy Immunology.[61]
2009 (September) Application Using gene therapy, researchers manage to give trichromatic vision to squirrel monkeys.[62]
2009 (November) Application 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.[63]
2010 Field development Critical components of the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 system are defined, which later forms the basis of gene editing.[13]
2010 (April) Field development 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.[64]
2010 (September) Application Gene therapy successfully treates 18-year-old male patient in France with beta-thalassemia.[65] France
2010–2011 Field development Cancer immunogene therapy using modified antigene, antisense/triple helix approach is introduced in South America in University of La Sabana, Bogota.[66][67] Colombia
2011 Drug Neovasculgen is registered in Russia as the first-in-class gene-therapy drug for treatment of peripheral artery disease, including critical limb ischemia.[68][51]
2012 Drug 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.[69][22][70]
2014 Field development Gene therapy clinical trials shows promise for inherited blood disorders, certain types of progressive blindness and HIV.[22][71]
2014 Literature Gerhard Bauer and Joseph S. Anderson publish Gene Therapy for HIV.[72]
2016 Literature Ravin Narain publishes Polymers and Nanomaterials for Gene Therapy.[73]
2017 Drug The United States Food and Drug Administration approves the first gene therapy, tisagenlecleucel (Kymriah), for refractory B-cell precursor acute lymphoblastic leukemia.[74] United States
2017 Literature Camiel J.F. Boon and Jan Wijnholds publish Retinal Gene Therapy: Methods and Protocols.[75]

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See also

External links

References

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