Gene therapy

Gene therapy is the therapeutic delivery of nucleic acid in a patient’s cells as a drug to treat disease. [1] The first attempt at human-modifying DNA Was Performed in 1980 by Martin Cline , drank the first successful nuclear gene transfer in humans, approved by the National Institutes of Health , Was Performed in May 1989. [2] The first therapeutic use of gene transfer as well as the first live insertion of human DNA into the nuclear genome was Performed by French Anderson in a trial starting in September 1990.

Between 1989 and February 2016, over 2,300 clinical trials Conducted HAD beens, more than half of ’em in Phase I . [3]

Not all medical procedures may be considered as a gene therapy. Bone marrow transplantation and organ transplants in general. [4] Gene therapy is defined by the precision of the procedure and the intention of direct therapeutic effects.


Gene therapy was conceptualized in 1972 by authors who urged caution before starting human gene therapy studies.

The first attempt, an unsuccessful one, was performed by Martin Cline on 10 July 1980. [5] [6] Cline claimed that gene therapy ( transplantation ) One of the genes in his patients has been active [7] and even if he is correct, it is unlikely that it will produce any significant beneficial effects of beta-thalassemia treatment .

After extensive research on animals throughout the 1980s and early 1990s, the first gene therapy was widely accepted as a success in the field of ADA – SCID . [8]

The first somatic treatment that produced a permanent genetic change was performed in 1993. [9]

This procedure has been reported to be somewhat unreliable in the media as a “parent of the baby,” although it is not the primary human genome and has little effect on an organism’s individual characteristics beyond their cells.

Gene therapy is a way to get a genetic problem at its source. The polymers are Either translated into proteins , interfere with target gene phrase , gold Possibly proper genetic mutations .

Reviews The most common form uses DNA That was encoded functional, therapeutic gene to replace a mutated gene. The polymer molecule is packaged within a ” vector “, which carries the molecule inside cells.

Early clinical failures led to dismissals of gene therapy. Clinical successes since 2006 regained researchers’ attention, as of 2014, it was still largely an experimental technique. [10] These include treatment of retinal diseases Leber’s congenital amaurosis [11] [12] [13] [14] and choroideremia , [15] X-linked SCID , [16] ADA-SCID, [17] [18] adrenoleukodystrophy , [19] chronic lymphocytic leukemia (CLL), [20] acute lymphocytic leukemia (ALL), [21] multiple myeloma ,[22]haemophilia , [18] and Parkinson’s disease . [23] Between 2013 and April 2014, US companies invested over $ 600 million in the field. [24]

The first commercial gene therapy, Gendicine , was approved in China in 2003 for the treatment of certain cancers. [25] In 2011 Neovasculgen was registered in Russia as the first-in-class gene-therapy drug for treatment of peripheral artery disease , including critical limb ischemia . [26] In 2012 Glybera , a treatment for a rare inherited disorder , became the first treatment for the European Union or the United States after its endorsement by the European Commission . [10] [27]


Following early advances in the genetic engineering of bacteria, cells, and small animals, the scientists started considering how to apply it to medicine. Two main approaches have been considered – replacing or disrupting defective genes. [28] Scientists focused on diseases caused by single-gene defects, such as cystic fibrosis , haemophilia , muscular dystrophy , thalassemia , and sickle cell anemia . Glybera treats one such disease, caused by a defect in lipoprotein lipase . [27]

DNA must be administered, reach the damaged cells, enter the cell and express or disrupt a protein. [29] Multiple delivery techniques have been explored. The initial approach incorporated DNA into an engineered virus to deliver the DNA into a chromosome . [30] [31] Naked DNA approaches have also been explored, especially in the context of vaccine development. [32]

Generally, efforts focused on administering a gene that causes a protein to be expressed. More recently, Increased understanding of nuclease function HAS led to more DNA Direct editing, using technical Such As zinc finger nucleases and CRISPR . The vector incorporates genes into chromosomes. The expressed nucleases then knock out and replace genes in the chromosome. As of 2014 these approaches involve removing cells from patients, editing a chromosome and returning the transformed cells to patients. [33]

Gene editing is a potential approach to the genome to treat genetic diseases, [34] viral diseases, [35] and cancer. [36] As of 2016 these approaches were still years of being medicine. [37] [38]

A duplex of crRNA and tracRRNA acts as a guide RNA to provide a specific gene modification based on the RNA 5 ‘upstream of the crRNA. Cas9 binds the tracrRNA and needs a DNA binding sequence (5’NGG3 ‘), which is called protospacer adjacent motif (PAM). After binding, Cas9 introduces a DNA double strand break, which is then followed by gene modification via homologous recombination (HDR) or non-homologous end-joining (NHEJ).

Cell types

Gene therapy can be classified into two types:


In somatic cell gene therapy (SCGT), the therapeutic genes are transferred to gamete , germ cell , gametocyte , or undifferentiated stem cell . Any such changes affect the individual patient only, and are not inherited by offspring . Somatic gene therapy Represents mainstream basic and clinical research, in qui therapeutic DNA (Either integrated in the genome or as an external episome or plasmid ) is used to treat disease.

Over 600 clinical trials utilizing SCGT are underway in the US. Most focus on severe genetic disorders, including immunodeficiencies , haemophilia , thalassemia , and cystic fibrosis . Such single gene disorders are good candidates for somatic cell therapy. The complete correction of a genetic disorder or the replacement of multiple genes is not yet possible. Only a few of the trials are in the advanced stages. [39]


In germline gene therapy (GGT), germ cells ( sperm or egg cells ) are modified by the introduction of functional genes into their genomes. Modifying a germ cell causes the organism’s cells to contain the modified gene. The change is therefore heritable and passed on to later generations. Australia, Canada, Germany, Israel, Switzerland, and the Netherlands [40] prohibit GGT for application in human beings, for technical and ethical reasons, including the possibility of future risks [40] and higher risks versus SCGT. [41]The US has no federal guidelines for the treatment of genetically modified diseases (beyond FDA regulations for therapies in general). [40] [42] [43] [44]


Main article: Vectors in gene therapy

The delivery of DNA into the cells can be accomplished by multiple methods . The two major classes are recombinant viruses (sometimes called biological nanoparticles or viral vectors) and naked DNA or DNA complexes (non-viral methods).


Main article: Viral vector

In order to replicate , viruses introduce their genetic material into the host cell, tricking the host’s cellular machinery by using it as blueprints for viral proteins. Retroviruses go a stage further by having their genetic material copied to the genome of the host cell. Scientists exploit this by substituting for a virus’s genetic material with therapeutic DNA. (The term ‘DNA’ may be an oversimplification, as some viruses contain RNA, and gene therapy could take this form.) A number of viruses have been used for human gene therapy, including retroviruses , adenoviruses , herpes simplex , vaccinia , and adeno-associated virus .[3] Like the genetic material (DNA or RNA) in viruses, therapeutic DNA can be conceived to be simply a degraded naturally orally (at least theoretically) to enter the host’s genome, becoming a permanent part of the host DNA in infected cells.


Non-viral methods present certain advantages over viral methods, such as large scale production and low host immunogenicity . However, non-viral methods are primarily produced at lower levels of transfection and gene expression, and thus lower therapeutic efficacy. Later technology remedied this deficiency citation needed ] .

Methods for non-viral gene therapy include the injection of naked DNA, electroporation , the gene gun , sonoporation , magnetofection , the use of oligonucleotides , lipoplexes, dendrimers, and inorganic nanoparticles.


Some of the unsolved problems include:

  • Short-lived nature – Before gene therapy can become a permanent cure for a condition, the therapeutic DNA has been introduced into the cells of the world. Problems with Integrating Therapeutic DNA in the Genome and the Rapid Depreciation. Patients require multiple treatments.
  • Immune response – Any time a foreign object is introduced into human tissues, the immune system is stimulated to attack the invader. Stimulating the immune system in a way that reduces gene therapy effectiveness is possible. The immune system ‘s response to viruses.
  • Problems with viral vectors – Viral vectors carry the risks of toxicity, inflammatory responses, and gene control and targeting issues.
  • Multigene disorders – Some Commonly Occurring disorders, Such As heart disease , high blood pressure , Alzheimer’s disease , arthritis , and diabetes , are affected by variations in multiple genes, qui complicate gene therapy.
  • Some therapies may breach the Weismann barrier (between soma and germ-line) protecting the testes, potentially modifying the germline, falling afoul of regulations in countries that prohibit the latter practice. [45]
  • Insertional mutagenesis – If the DNA is integrated in a sensitive spot in the genome, for example in a tumor suppressor gene , the therapy could induce a tumor . This study was conducted in the most recent clinical trials of X-linked patients in whom hematopoietic stem cells were transduced with a transgene receptor using a retrovirus , and this led to the development of T cell leukemia in 3 of 20 patients. . [46] [47]One possible solution is to add a functional tumor suppressor gene to the DNA to be integrated. This may be problematic since the DNA is, the harder it is to integrate into cell genomes. CRISPR technology enables researchers to make much more accurate genome changes at exact locations. [48]
  • Cost – Alipogene tiparvovec Gold Glybera, for example, was $ 1.6 million per patient, was reported in 2013 to be the world’s most expensive drug. [49] [50]


Three patients have been reported in gene therapy trials, putting the field under close scrutiny. The first was that of Jesse Gelsinger in 1999. Jesse Gelsinger died because of immune rejection response. [51] One X-SCID patient died of leukemia in 2003. [8] In 2007, a rheumatoid arthritis patient died from an infection; the subsequent investigation that the death was not related to gene therapy. [52]


1970s and earlier

In 1972 Friedmann and Roblin authored a paper in Science titled “Gene therapy for human genetic disease?” [53] Rogers (1970) was cited for proposing that exogenous good DNA be used to replace the defective DNA in those who suffer from genetic defects. [54]


In 1984, a retrovirus vector system was designed that could possibly insert foreign genes into mammalian chromosomes. [55]


The first approved gene therapy clinical research in the US took place on September 14, 1990, at the National Institutes of Health (NIH), under the direction of William French Anderson . [56] Four-year-old Ashanti DeSilva has been treated with ADA – SCID , a severe immune system deficiency. The effects were temporary, but successful. [57]

Cancer gene therapy was introduced in 1992/93 (Trojan et al., 1993). [58] The treatment of glioblastoma multiforme, the malignant brain tumor whose outcome is always fatal, was done using a vector expressing antisense IGF-I RNA (clinical trial approved by NIH protocolno.1602 November 24, 1993, [59] and by the FDA in 1994). This therapy also represents the beginning of cancer immunogenic therapy, which is an effective treatment for the anti-tumor mechanism of IGF-I antisense, which is related to strong immune and apoptotic phenomena.

In 1992 Claudio Bordignon , working at the Vita-Salute San Raffaele University , performed the first gene therapy procedure using hematopoietic stem cells as vectors to deliver genes to correct hereditary diseases . [60] In 2002 this work was published in the first successful gene therapy for adenosine deaminase deficiency (ADA-SCID). The success of a multi-center trial for SCID ( severe combined immune deficiency)or “bubble boy” disease) from 2000 and 2002, was questioned when two of the ten children in the Paris trial developed a leukemia-like condition. Clinical trials were halted in 2002, but the United States, France, Italy, and Germany. [61]

In 1993 Andrew Gobea was born with SCID following prenatal genetic screening . Blood was removed from his mother ‘s placenta and umbilical cord immediately after birth, to acquire stem cells. The allele that codes for adenosine deaminase (ADA) was obtained and inserted into a retrovirus. Retroviruses and stem cells were mixed, after which the viruses inserted into the stem cell chromosomes. Stem cells containing the working ADA gene were injected into Andrew’s blood. Injections of the ADA enzyme were also given weekly. For four years T cells (white blood cells), produced by stem cells, made ADA enzymes using the ADA gene. After years more treatment was needed.quote needed ]

Jesse Gelsinger’s death in 1999 impeded gene therapy research in the US. [62] [63] As a result, the FDA has suspended several clinical trials pending the reevaluation of ethical and procedural practices. [64]


The modified cancer gene therapy strategy of antisense IGF-I RNA (NIH # 1602) [59] using antisense / triple helix anti-IGF-I was registered in 2002 by Wiley Gene Therapy Clinical Trial – # 635 and # 636. has shown promising results in the treatment of six different malignant tumors: glioblastoma, cancers of liver, colon, prostate, uterus, and ovary (Collaborative NATO Science Program on Gene Therapy USA, France, Poland No. LST 980517 conducted by J. Trojan) (Trojan et al., 2012). This anti-gene antisense / triple helix therapy has proven to be effective, due to the mechanism of IGF-I expression on translation and transcription levels, enhancing anti-tumor immunity and apoptotic phenomena.


Sickle-cell disease can be treated in mice. [65] The mice – which have essentially the same causes of human cases – used in viral vector to induce production of fetal hemoglobin (HbF). In humans, the use of hydroxyurea to stimulate the production of HbF only alleviates sickle cell symptoms. The researchers showed this treatment to be more permanent means to increase HbF production. [66]

A new gene therapy approach repaired errors in messenger RNA derived from defective genes. This technique has the potential to treat thalassemia , cystic fibrosis and some cancers. [67]

Researchers created liposomes 25 nanometers across that can carry therapeutic DNA through pores in the nuclear membrane . [68]


In 2003 a research team inserted into the brain for the first time. They used liposomes coated in a polymer called polyethylene glycol , which, unlike viral vectors, are small enough to cross the blood-brain barrier . [69]

Short pieces of double-stranded RNA (short, interfering RNAs or siRNAs ) are used by cells to degrade RNA of a particular sequence. If a siRNA is designed to match the RNA copied from a faulty gene, then the abnormal protein product will be produced. [70]

Gendicin is a cancer gene that delivers the tumor suppressor gene p53 using an engineered adenovirus . In 2003, it was approved in China for the treatment of head and neck squamous cell carcinoma . [25]


In March, 2009, published in the literature on the treatment of X-linked chronic granulomatous diseases , a disease which affects myeloid cells and the immune system . The study is the first to show that gene therapy can treat the myeloid system. [71]

In May a team reported a way to prevent the immune system from rejecting a newly delivered gene. [72] Similar to organ transplantation , gene therapy has been plagued by this problem. The immune system is usually new to the world, and the cells carrying it. The microinspired microRNAs . This natural function selectively obscured their therapeutic gene in immune systems and protected it from discovery. Mice infected with the gene containing an immune-cell microRNA target sequence did not reject the gene.

Metastatic melanoma in two patients using killer T cells genetically retargeted to attack the cancer cells. [73]

In November Researchers Reported 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 . In a phase I clinical trial , five subjects with chronic HIV infection who had failed to respond to at least two antiretroviral regimens were treated. A single intravenous infusion of autologous CD4T cells genetically modified with VRX496 was well tolerated. All patients had stable or decreased viral load; Four of the five patients had stable or increased CD4 cell counts. All five patients had stable or increased immune response to HIV antigens and other pathogens . This was the first evaluation of a vectorized vector in a US human clinical trial. [74] [75]


In May researchers announced the first gene therapy trial for inherited retinal disease . The first operation was conducted on 23-year-old British male, Robert Johnson, in early 2007. [76]


Main article: Gene therapy of the human retina

Leber’s congenital amaurosis is an inherited blinding disease caused by mutations in the RPE65 gene. The results of a small clinical trial in children were published in April. [11] Delivery of recombinant adeno-associated virus (AAV) carrying RPE65 yielded positive results. In May two more groups reported positive results in independent clinical trials. In all three clinical trials, patients with functional vision without apparent side-effects. [11] [12] [13] [14]


In September, researchers were able to give trichromatic vision to squirrel monkeys . [77] In November 2009, researchers halted 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. [78]



An April paper reported that gene therapy addressed achromatopsia (color blindness) in dogs by targeting cone photoreceptors. Cone function and day vision were restored for at least 33 months in two young specimens. The therapy was less efficient for older dogs. [79]

In September it was announced that an 18-year-old male patient in France with beta-thalassemia was successfully treated. [80] Beta-thalassemia major is an inherited blood disease in which beta haemoglobin is absent and is subject to regular lifelong blood transfusions . [81] The technique used in lentiviral vector to transduce the human β-globin gene into purified blood and marrow cells obtained from the patient in June 2007. [82] The patient’s hemoglobin levels were stable at 9 to 10 g / dL. About a third of the hemoglobin contained in the viral vector and blood transfusions were not needed.[82] [83] Further clinical trials were planned. [84] Bone marrow transplants are the only cure for thalassemia, but 75% of patients do not find a matching donor. [83]

Immunogenic cancer using modified anti – gene, antisense / triple helix approach was introduced in South America in 2010/11 in Sabana University, Bogota (Ethical Committee 14 December 2010, P – 004-10). Considering the ethical aspect of IGF-I, the IGF-I expressing tumors ie lung and epidermis cancers, were treated (Trojan et al., 2016). [85] [86]


In 2007 and 2008, a man ( Timothy Ray Brown ) was diagnosed with HIV by repeated hematopoietic stem cell transplantation (see also allogeneic stem cell transplantation , allogeneic bone marrow transplantation , allotransplantation ) with double-delta-32 mutations that were mutable to the CCR5 receptor. This cure Was accepted by the medical community in 2011. [87] It required full removal of Existing bone marrow , qui is very debilitating.

Chronic lymphocytic leukemia (CLL) has been confirmed in recent years . The therapy used genetically modified cells to express CD19 protein to fight disease. [20] In 2013, the researchers announced that 26 of 59 patients had achieved complete remission and the original patient had remained tumor-free. [88]

Human HGF plasmid DNA therapy of cardiomyocytes is being examined as a potential treatment for coronary artery disease as well as for the treatment of myocardial infarction . [89] [90]

In 2011 Neovasculgen was registered in Russia as the first-in-class gene-therapy drug for treatment of peripheral artery disease , including critical limb ischemia ; it delivers the gene encoding for VEGF . [91] [26] Neovasculogen is a plasmid encoding the CMV promoter and the amino acid 165 form of VEGF . [92] [93]


The FDA approved Phase 1 clinical trials on thalassemia major patients in the US for 10 participants in July. [94] The study was expected to continue until 2015. [95]

In July 2012, the European Medicines Agency recommended approval of a gene therapy treatment for the first time in Europe or the United States. The treatment used Alipogene tiparvovec (Glybera) to compensate for lipoprotein lipase deficiency , which can cause severe pancreatitis . [96] The recommendation was endorsed by the European Commission in November 2012 [10] [27] [97] [98] and commercial rollout began in late 2014. [99] Alipogene tiparvovec was expected to cost $ 1.6 million per treatment in 2012 , [100] revised to $ 1 million in 2015, [101]making it the most expensive medicine in the world at the time. [102] As of 2016, only one person had been treated with drug. [103]

In December 2012 it Was Reported That 10 of 13 patients with multiple myeloma Were in remission “or very close to it” three months after-being white injected with a treatment Involving genetically engineered T cells to target proteins NY-ESO-1 and LAGE-1 , which exists only on cancerous myeloma cells. [22]


In March Researchers Reported That three of five adult subjects Who HAD acute lymphocytic leukemia (ALL) HAD-been in remission for five months to two Years After being white Treated with genetically modified T cells qui attacked This cells with CD19 genes on Their area, ie all B- cells , cancerous or not. The researchers believed that the immune system would make normal T-cells and B-cells after a couple of months. They were also given bone marrow. One patient relapsed and died and died of unrelated to the disease. [21]

Following encouraging Phase 1 trials, in April, researchers announced they were starting Phase 2 clinical trials (called CUPID2 and SERCA-LVAD) on 250 patients [104] and several hospitals to fight heart disease . The therapy was designed to increase the levels of SERCA 2, a protein in heart muscles, improving muscle function. [105] The FDA granted this breakthrough Therapy Designation to accelerate the trial and approval process. [106] In 2016 it was reported that no improvement was found from the CUPID 2 trial. [107]

In July 2007, the results of this study were reported to have been treated with a partial follow-up. Three of the children had metachromatic leukodystrophy , which causes children to lose cognitive and motor skills. [108] The other children had Wiskott-Aldrich syndrome , which leaves them to open infection, autoimmune diseases, and cancer. [109] Wiskott-Aldrich syndrome was also reported as promising. [110] [111]

In October Researchers Reported That two children born with adenosine deaminase severe combined immunodeficiency disease ( ADA-SCID ) HAD beens Treated with genetically engineered stem cells 18 months Previously Their immune systems and That Were showing signs of full recovery. Another three children were making progress. [18] In 2014 a further 18 children with ADA-SCID were cured by gene therapy. [112] ADA-SCID children have no functioning immune system and are known to “bubble children.” [18]

They also reported six haemophilia sufferers in early 2011 using an adeno-associated virus. Over two years were all produced . [18] [113]


In January researchers reported that six choroideremia patients had been treated with adeno-associated virus with a copy of REP1 . Over a six-month to two-year period all had their sight. [114] [115] By 2016, 32 patients had been treated with positive results and long-lasting hope. [15] Choroideremia is an inherited genetic eye disease with no approved treatment, leading to loss of sight.

In March researchers reported that HIV has been treated with a rare mutation ( CCR5 deficiency) that is known to protect against HIV with promising results. [116] [117]

Clinical trials of gene therapy for sickle cell disease Were started in 2014. [118] [119] There is a need for high quality randomized controlled trials Assessing the Risks and benefits Involved with gene therapy for people with sickle cell disease. [120]


In February LentiGlobin BB305 , a gene therapy treatment undergoing clinical trials for treatment of thalassemia- enhanced FDA beta “breakthrough” status after several patients were able to treat the frequent blood transfusions usually required to treat the disease. [121]

In March researchers delivered a recombinant gene encoding a broadly neutralizing antibody to monkeys infected with simian HIV ; the monkeys’ cells produced the antibody , which cleared them of HIV. The technique is named immunoprophylaxis by gene transfer (IGT). Animal tests for antibodies to ebola, malaria, influenza, and hepatitis were underway. [122] [123]

In March, scientists, including an inventor of CRISPR , Jennifer Doudna , urged a worldwide moratorium on germline gene therapy, writing “scientists should avoid even attempting,” in lax jurisdictions, “germline genome modification for clinical application in humans” until the full implications “are discussed among scientific and governmental organizations “. [124] [125] [126] [127]

In October, the researchers announced that they had treated a baby girl, Layla Richards, with an experimental treatment using donor T-cells genetically engineered using TALEN to attack cancer cells. One year after the treatment of cancer (a highly aggressive form of acute lymphoblastic leukemia [ALL]). [128] Children with a highly aggressive ALL have a very poor prognosis and have not been treated properly before treatment. [129]

In December, scientists of major world academies called for a moratorium on inheritable human genetics, including those related to CRISPR-Cas9 technologies [130] but that basic research including embryo gene editing should continue. [131]


In the Committee for Medicinal Products for Human Use of the European Medicines Agency endorsed a gene therapy treatment called Strimvelis [132] [133] and the European Commission approved it in June. [134] ADA-SCID and who have no functioning immune system – sometimes called “bubble baby” disease. This was the second gene therapy treatment approved in Europe. [135]

In October, Chinese scientists reported that they had started a trial to genetically modify T-cells from 10 adult patients with lung cancer and reinject the modified T-cells back into their bodies to attack cancer cells. The T-cells had the PD-1 protein (which stops or slows the immune response) removed using CRISPR-Cas9. [136] [137]

A 2016 Cochrane is a topical cystic fibrosis transmembrane conductance regulator (CFTR) gene therapy does not support its clinical use as a mist in the lungs to treat cystic fibrosis patients with lung infections. One of the four trials has found weak evidence that liposome-based CFTR gene transfer therapy may lead to a small respiratory improvement for people with CF. This weak evidence is not enough to make a clinical recommendation for routine CFTR gene therapy. [138]


In February Kite Pharma announced results from a clinical trial of CAR-T cells in a hundred people with advanced non-Hodgkin lymphoma . [139]

In March, French scientists reported on clinical research on gene therapy to treat sickle-cell disease . [140]

In August, the FDA approved tisagenlecleucel for acute lymphoblastic leukemia. [141] Tisagenlecleucel is an adoptive cell transfer therapy for B-cell acute lymphoblastic leukemia ; T cells are a genetically engineered receptor that has a specific T-cell receptor (a chimeric T cell receptor, or ” CAR-T “) that is reactive to cancer, and is administered back to the person. The T cells are engineered to target a protein called CD19 that is common on B cells. This is the first form of therapy approved in the United States. In October, a similar therapy called axicabtagene ciloleucel was approved for lymphoma .

In a patient with an adeno-associated virus with clotting factor VIII to treat a haemophilia A patients were published. Six of the seven patients on the high dose diet VIII to normal levels. The low and medium dose regimen had no effect on the patient’s blood clotting levels. [142] [143]

In December, the FDA approved Luxturna , the first in vivo gene therapy, for the treatment of blindness to Leber’s congenital amaurosis . [144] The cost of this treatment was speculated to be one million US dollars. [145] CRISPR gene editing technology has also been used to treat deafness due to the DFNA36 mutation, which also affects humans. [146]

Speculative uses

Speculated uses for gene therapy include:


Gene Therapy techniques have the potential to provide alternative treatments for those with infertility. Recently, successful experimentation on mice has proven that fertility can be restored by using the gene therapy method, CRISPR. [147] Spermatogenical stem cells from another organism were transplanted into the testes of an infertile male mouse. The stem cells re-established spermatogenesis and fertility. [148]

Gene doping

Main article: Gene doping

Athletes might adopt gene therapy technologies to improve their performance. [149] Gene doping is not known to occur, but multiple gene therapies may have such effects. Kayser et al. argue that gene doping could level the playing field if all athletes receive equal access. Critics claim that any therapeutic intervention for non-therapeutic / enhancement purposes compromises the ethical foundations of medicine and sports. [150]

Human genetic engineering

See also: Germinal choice technology and Human germline engineering

Genetic engineering could be used to cure diseases, but also to change physical appearance, metabolism , and even improve physical capabilities and mental faculties such as memory and intelligence . Ethical claims about germline engineering include beliefs that every single fetus has a right to remain genetically unmodified, that parents hold the right to genetically modify their offspring, and that every child has the right to be free from preventable diseases. [151] [152] [153] For parents, genetic engineering could be seen as another child enhancement technique to add to diet, exercise, education, training, cosmetics, and plastic surgery. [154][155] Another theorist claims that moral concerns limit but do not prohibit germline engineering. [156]

Possible regulatory schemes include a complete ban, provision to everyone, or professional self-regulation. The American Medical Association’s Advisory Board on Ethical and Judicial Affairs states that “(2) no trade-off with other characteristics and (3) equal access to the genetic technology, irrespective of income or other socioeconomic characteristics. ” [157]

As early as in the history of biotechnology as 1990, there have been some studies on the use of these new tools, [158] and such concerns have continued as technology progressed. [159] [160] With the advent of new technologies like CRISPR , in March 2015 group of scientists urged a worldwide moratorium is clinical use of gene editing technology to edit the human genome in a way That can be inherited. [124] [125] [126] [127] In April 2015, Researchers Sparked controversy When They Reported results of basic research to edit theDNA of non-viable human embryos using CRISPR. [147] [161] A committee of the American National Academy of Sciences and National Academy of Medicine gave qualified backing to human genome editing in 2017 [162] [163] ounce answers-have-been found to safety and efficiency problems “goal only for serious conditions under stringent oversight. ” [164]


Regulations covering genetic modification are part of the general guidelines about human-involved biomedical research. There are no international treaties which are legally binding in this area, but there are recommendations for national laws from various bodies.

The Helsinki Declaration (Medical Principles for Medical Research Involving Human Subjects) was prepared by the World Medical Association’s General Assembly in 2008. The Statement on Gene Therapy Research initiated by the Human Genome Organization (HUGO) in 2001 provides a legal basis for all countries. HUGO’s document emphasizes human freedom and adherence to human rights, and offers recommendations for somatic gene therapy, including the importance of recognizing public concerns about such research. [165]

United States

No federal legislation lays out protocols or restrictions on human genetic engineering. The FDA and the NIH’s Recombinant DNA Advisory Committee , the Department of Health and Human Services . Researchers seeking federal funds for an investigational new drug application, commonly known for the protection of human subjects. [166]

NIH serves as the main gene therapy regulator for federally funded research. Privately funded research is advised to follow these regulations. NIH provides funding for research that develops or develops genetic engineering techniques and to evaluate the ethics and quality in current research. The NIH maintains a mandatory registry of human genetic engineering research that includes all funded projects.

An NIH advisory committee published a set of guidelines on gene manipulation. [167] The guidelines discuss the safety of test subjects and the various types of genetic modifications. Several sections specifically pertain to human genetic engineering, including Section III-C-1. This section discusses the need for further study and other aspects of clinical trials. [168] The protocol for a clinical trial must be approved by the NIH Recombinant DNA Advisory Committee prior to any clinical trial beginning; this is different from any other kind of clinical trial. [167]

As with other kinds of drugs, the FDA regulates the quality and safety of gene therapy products and is used clinically. Therapeutic alteration of the human genome falls under the same regulatory requirements as any other medical treatment. Research involving human subjects, such as clinical trials , must be reviewed by the FDA and an Institutional Review Board . [169] [170]

Popular culture

Gene therapy is the basis for the plotline of the film I Am Legend [171] and the TV show Will Gene Therapy Change the Human Race? [172] It is also used in Stargate as a way of enabling humans to use Ancient technology. [173]

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