In the field of medicine, gene therapy (also called transfer of human genes ) is the delivery of therapeutic nucleic acid into patient cells as a cure for disease. The first attempt to modify human DNA was conducted in 1980 by Martin Cline, but the first successful transfer of human nucleic genes, approved by the National Institutes of Health, was conducted in May 1989. The use of first gene transfer therapy and the first direct insertion of human DNA into nuclear genome performed by Anderson France in trials began in September 1990.
Between 1989 and February 2016, more than 2,300 clinical trials have been conducted, more than half of them in phase I.
Not all medical procedures that introduce changes to the patient's genetic makeup can be regarded as gene therapy. Bone marrow transplant and organ transplant in general have been found to introduce foreign DNA in patients. Gene therapy is defined by the precision of the procedure and the intent of a direct therapeutic effect.
Video Gene therapy
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Gene therapy was conceptualized in 1972, by authors who urged caution before starting human gene therapy studies.
The first, unsuccessful attempt at gene therapy (as well as the first case of medical transfer of foreign genes to humans excluding organ transplants) was performed by Martin Cline on July 10, 1980. Klein claimed that one of the genes in his patient was active six months later, though he never publish this data or it has been verified and even if he is correct, it is unlikely that it produces a significant beneficial effect treating beta-thalassemia.
Following extensive animal studies throughout the 1980s and experimental bacterial genes in 1989 in humans, the first gene therapy that was widely accepted as a success was demonstrated in an experiment that began on September 14, 1990, when Ashi DeSilva was treated for ADA-SCID.
The first somatic treatment that produced permanent genetic changes was done in 1993.
Gene therapy is a way to correct genetic problems at the source. The polymer is either translated to a protein, interfering with the expression of the target gene, or it may be true of a genetic mutation.
The most common forms use DNA that encodes functional and therapeutic genes to replace mutated genes. Polymer molecules are packaged in "vectors", which carry molecules inside the cell.
Early clinical failure led to the dismissal of gene therapy. Clinical success since 2006 has attracted the attention of researchers, though by 2014, most still is an experimental technique. These include treatment of Leber's inherited congenital amabilic disease and chloroideremia, X-linked SCID, ADA-SCID, adrenoleukodystrophy, chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), multiple myeloma, haemophilia, and Parkinson's disease. Between 2013 and April 2014, US companies invested more than $ 600 million in the field.
The first commercial gene therapy, Gendicine, was approved in China in 2003 for the treatment of certain cancers. In 2011 Neovasculgen was registered in Russia as the first gene therapy drug in its class for the treatment of peripheral arterial disease, including critical limb ischemia. In 2012 Glybera, a treatment for rare heritage disorders, became the first approved treatment for clinical use in either Europe or the United States after approval by the European Commission.
Maps Gene therapy
Approach
Following early advances in genetic engineering of bacteria, cells, and small animals, scientists began to consider how to apply it to drugs. Two major approaches are considered - replacing or disrupting the damaged genes. Scientists focus on diseases caused by single gene defects, such as cystic fibrosis, hemophilia, muscular dystrophy, thalassemia, and sickle cell anemia. Glybera treats one such disease, caused by lipoprotein lipase defect.
DNA must be given, reaching damaged cells, entering cells and expressing or interfering with proteins. Some delivery techniques have been explored. The initial approach incorporates DNA into the engineered virus to deliver DNA into the chromosomes. The nude DNA approach has also been explored, especially in the context of vaccine development.
Generally, efforts are focused on giving genes that cause the proteins needed to be expressed. More recently, improved understanding of nuclease function has led to more direct DNA editing, using techniques such as nucleation of the zinc radius and CRISPR. Vectors combine genes into chromosomes. The expressed nuklease then paralyzes and replaces the genes on the chromosome. In 2014 this approach involves removing cells from patients, editing the chromosomes and returning the altered cells to the patient.
Gene editing is a potential approach to changing the human genome to treat genetic diseases, viral diseases, and cancers. By 2016 this approach is still years away from drugs.
Cell type
Gene therapy can be classified into two types:
Somatic
In somatic cell gene therapy (SCGT), therapeutic genes are transferred to cells other than gametes, germ cells, gametocytes, or undifferentiated stem cells. Such modifications only affect individual patients, and are not inherited by offspring. Somatic gene therapy is a major baseline and clinical study, in which therapeutic DNA (either integrated in the genome or as an external episome or plasmid) is used to treat the disease.
More than 600 clinical trials using SCGT are underway in the US. Much of the focus is on severe genetic disorders, including immunodeficiency, hemophilia, thalassemia, and cystic fibrosis. Such single gene disorders are good candidates for somatic cell therapy. Complete correction of genetic abnormalities or replacement of some genes is not yet possible. Only a few trials are in the advanced stages.
Germline
In germline gene therapy (GGT), germ cells (sperm or ovum) are modified by the introduction of functional genes into their genomes. Modifying germ cells causes all the cells of the organism to contain the modified gene. Therefore change is inherited and passed on to the next generation. Australia, Canada, Germany, Israel, Switzerland and the Netherlands prohibit GGT to be applied to humans, for technical and ethical reasons, including lack of knowledge about possible risks for future generations and higher risks than SCGT. The US has no federal controls specifically addressing human genetic modification (beyond FDA regulations for general therapy).
Vector
DNA delivery into cells can be solved by several methods. The two major classes are recombinant viruses (sometimes called biological nanoparticles or viral vectors) and naked DNA or DNA complexes (non-viral methods).
Virus
To replicate, the virus introduces their genetic material into the host cell, tricking the host's home machine into using it as a blueprint for viral proteins. Retroviruses go further by having their genetic material copied into the host cell genome. Scientists exploit this by replacing viral genetic material with therapeutic DNA. (The term 'DNA' may be oversimplified, as some viruses contain RNA, and gene therapy can take this form as well.) A number of viruses have been used for human gene therapy, including retroviruses, adenoviruses, herpes simplex, vaccinia, and adeno-related viruses. Like genetic material (DNA or RNA) in viruses, therapeutic DNA can be designed to serve only as a temporary blueprint while degrading naturally or (at least theoretically) to enter the host genome, becoming a permanent part of host DNA in the infected body. cell.
Non-viral methods provide certain advantages over viral methods, such as large-scale production and low host immunogenicity. However, non-viral methods initially resulted in lower levels of transfection and gene expression, thereby decreasing therapeutic efficacy. Technology then fixes this shortcoming.
Methods for non-viral gene therapy include nude DNA injections, electroporation, gun genes, sonoporation, magnetophysiology, use of oligonucleotides, lipoplexes, dendrimers, and inorganic nanoparticles.
Hurdles
Some unsolved issues include:
- Short-lived properties - Before gene therapy can be a permanent remedy for a condition, therapeutic DNA inserted into target cells should remain functional and cells containing therapeutic DNA should be stable. The problem with integrating therapeutic DNA into the genome and the rapid nature of dividing many cells prevents it from achieving long-term benefits. Patient needs a lot of care.
- Immune response - Every time a foreign object is inserted into human tissue, the immune system is stimulated to attack the invaders. Stimulating the immune system in ways that reduce the effectiveness of gene therapy is possible. An enhanced immune system response to previously observed viruses reduces the effectiveness of repeated treatments.
- Problems with viral vectors - Viral vectors carry the risk of toxicity, inflammatory responses, and gene control and targeting problems. Multigene Disorders - Some common disorders, such as heart disease, high blood pressure, Alzheimer's disease, arthritis, and diabetes, are affected by variations in some genes, which complicate gene therapy.
- Some therapies may break the Weismann barrier (between soma and germ-line) protect the testes, potentially modifying germline, breaking the rules in countries that prohibit the latter practice.
- insersional mutagenesis - If DNA is integrated in sensitive sites in the genome, for example in tumor suppressor genes, therapy may induce tumors. This has occurred in clinical trials for X-linked joint X-linked immunodeficiency (X-SCID) patients, where hematopoietic stem cells were transduced with corrective transgenes using retroviruses, and this led to the development of T cell leukemia in 3 of 20 patients.. One possible solution is to add a functional tumor suppressor gene to the DNA for integration. This may be problematic because the longer the DNA, the harder it is to integrate into the cell genome. CRISPR technology allows researchers to make more precise genome changes in the right location.
- Cost - Alipogene tiparvovec or Glybera, for example, at a cost of $ 1.6 million per patient, reported in 2013 to be the world's most expensive drug.
Death
Three patient deaths have been reported in gene therapy trials, placing this field under strict supervision. The first was Jesse Gelsinger in 1999. Jesse Gelsinger died of an immune rejection reaction. One X-SCID patient died of leukemia in 2003. In 2007, a patient with rheumatoid arthritis died of infection; subsequent investigations concluded that death was not associated with gene therapy.
History
1970s and earlier
In 1972 Friedmann and Roblin wrote a paper on Science titled "Gene therapy for human genetic disease?" Rogers (1970) is quoted to suggest that exogenous good DNA is used to replace damaged DNA in those with genetic defects.
1980s
In 1984 a retrovirus vector system was designed that could efficiently incorporate foreign genes into mammalian chromosomes.
1990s
The first US approved gene therapy clinical study took place on September 14, 1990, at the National Institutes of Health (NIH), under the direction of William French Anderson. Ashanti DeSilva, four years old, received treatment for a genetic defect that made her suffer from ADA-SCID, a severe immune system deficiency. The damaged gene from the patient's blood cells is replaced by a functional variant. Ashanti's immune system is partially restored by therapy. Production of the lost enzyme is temporarily stimulated, but new cells with functional genes are not produced. She leads a normal life just with a routine injection done every two months. The effect was successful, but temporary.
Cancer gene therapy was introduced in 1992/93 (Trojan et al., 1993). Treatment of glioblastoma multiforme, a malignant brain tumor whose results are always fatal, was performed using a vector expressing the antisense IGF-I RNA (a clinical trial approved by the NIH protocol no.1602 24 November 1993, and by the FDA in 1994). This therapy is also the beginning of cancer immunogene therapy, a treatment that proved effective because of the anti-tumor mechanism of IGF-I antisense, which is associated with a strong immune and apoptotic phenomenon.
In 1992, Claudio Bordignon, working at Vita-Salute University of San Raffaele, performed the first gene therapy procedure using hematopoietic stem cells as vectors to produce genes intended to correct hereditary diseases. In 2002 this work led to the successful publication of the first successful gene therapy therapy for adenosine deaminase (ADA-SCID) deficiency. The success of multi-center trials to treat children with SCID (severe combined immune deficiency or "baldness" disease) from 2000 and 2002, is questionable when two of the ten children treated in central Paris experiment develop conditions such as leukemia. Clinical trials were suspended in 2002, but continued after protocol regulatory review in the US, UK, France, Italy, and Germany.
In 1993 Andrew Gobea was born with SCID after prenatal genetic screening. Blood is removed from the mother's placenta and the cord immediately after birth, to obtain stem cells. The allele that encodes adenosine deaminase (ADA) is obtained and fed into the retrovirus. Retroviruses and stem cells are mixed, once viruses are inserted into the stem cell's chromosomes. Stem cells containing an ADA gene that works are injected into the blood of Andrew. Injections of ADA enzyme are also given every week. For four years T cells (white blood cells), produced by stem cells, make ADA enzymes using the ADA gene. After four years more care is required.
The death of Jesse Gelsinger in 1999 inhibited gene therapy research in the US. As a result, the FDA suspends some clinical trials while awaiting re-evaluation of ethical and procedural practices.
2000s
The IGF-I RNA (NIH n? 1602) antisense-modified antisense gene therapy strategy using the anti-IGF-I antisense/triple helix was enrolled in 2002 by clinical trials of Wiley-gene therapy. 635 and 636. This approach has shown promising results in the treatment of six distinct malignant tumors: glioblastoma, liver cancer, colon, prostate, uterus, and ovary (NATO Science Program Collaboration on Gene Therapy USA, France, Poland n? LST 980517 performed by J. Trojan) (Trojan et al., 2012). Antisense antisense/triple helix therapy is proven to be efficient, because the mechanism stops simultaneously the expression of IGF-I at the level of translation and transcription, strengthening the immune anti-tumor and apoptotic phenomenon.
2002
Sickle cell disease can be treated in mice. Mice - which basically have the same defects that cause human cases - use viral vectors to induce the production of fetal hemoglobin (HbF), which usually ceases to be produced soon after birth. In humans, the use of hydroxyurea to stimulate HbF production to temporarily relieve sickle cell symptoms. The researchers showed this treatment to be a more permanent means of increasing therapeutic HbF production.
The new gene therapy approach improves errors in carrier RNAs from damaged genes. This technique has the potential to treat thalassemia, cystic fibrosis and some cancers.
Researchers created 25-nanometer liposomes that can carry therapeutic DNA through the pores in nuclear membranes.
2003
In 2003 the research team inserted the gene into the brain for the first time. They use polymer-coated liposomes called polyethylene glycol, which unlike viral vectors, is small enough to cross the blood-brain barrier.
Short-stranded strands of short strands (short, interfering RNAs or siRNAs) are used by cells to decrease RNA from a particular sequence. If siRNA is designed to match the RNA copied from the wrong gene, then the abnormal protein product of that gene will not be produced.
Gendicine is a cancer-gene therapy that provides p53 tumor suppressor genes using engineered adenoviruses. In 2003, it was approved in China for the treatment of squamous cell carcinoma of the head and neck.
2006
In March the researchers announced the successful use of gene therapy to treat two adult patients for chronic granulomatous disease linked X, a disease that affects the myeloid cells and damages the immune system. This study is the first to show that gene therapy can treat the myeloid system.
In May, a team reported a way to prevent the immune system from rejecting the newly transmitted genes. Similar to organ transplants, gene therapy has been disrupted by this problem. The immune system usually recognizes the new gene as a foreign object and rejects the cell that carries it. This study utilizes a newly discovered gene network that is governed by molecules known as microRNAs. These natural functions selectively obscure their therapeutic genes in immune system cells and protect them from discovery. Mice infected with genes containing immune cell microRNA target sequences did not reject the gene.
In August, scientists managed to treat metastatic melanoma in two patients who used killer T cells that were genetically reinforced to attack cancer cells.
In November researchers reported on the use of VRX496, gene-based immunotherapy for HIV treatment using lentiviral vectors to deliver antisense genes to the HIV envelope. In phase I clinical trials, five subjects with chronic HIV infection who failed to respond to at least two ART regimens were treated. An intravenous infusion of autologous genetically modified CD4 T cells with VRX496 was well tolerated. All patients had a stable or decreased viral load; four out of five patients had stable or elevated CD4 T-cell counts. The five patients had a stable or increased immune response against HIV antigens and other pathogens. This is the first evaluation of the lentiviral vector given in US human clinical trials.
2007
In May the researchers announced the first gene therapy trial for inherited retinal disease. The first operation was performed on 23-year-old British man, Robert Johnson, in early 2007.
2008
Leber's congenital amaurosis is a heritable hereditary disease caused by mutations in the RPE65 gene. Small clinical trial results in children were published in April. Delivery of recombinant adeno-associated virus (AAV) carrying RPE65 yielded positive results. In May, two more groups reported positive results in independent clinical trials using gene therapy to treat the condition. In all three clinical trials, the patient restored functional vision without obvious side effects.
2009
In September the researchers were able to provide trichromatic vision to a squirrel monkey. In November 2009, researchers stopped a fatal genetic disorder called adrenoleukodystrophy in two children using a lentivirus vector to produce a functioning ABCD1 version, a mutated gene in the disorder.
2010s
2010
An April paper reported that gene therapy is aimed at achromatopsia (color blindness) in dogs by targeting cone photoreceptors. The cone function and day vision are restored for at least 33 months in two young specimens. The therapy is less efficient for older dogs.
In September it was announced that an 18-year-old male patient in France with major beta-thalassemia was successfully treated. Beta-thalassemia major is a blood-inherited disease in which beta hemoglobin is lost and the patient relies on lifelong blood transfusions on a regular basis. This technique used a lentiviral vector to transduct human ÃÆ'Ÿ-globin gene into blood cells and purified marrow obtained from patients in June 2007. The patient's hemoglobin level was stable at 9 to 10 g/dL. About one-third of hemoglobin contains forms introduced by viral vectors and blood transfusion is not required. Further clinical trials are planned. Bone marrow transplantation is the only cure for thalassemia, but 75% of patients do not find a suitable donor.
Cancer immunogene therapy using modified antigen, antisense/triple helix approach was introduced in South America in 2010/11 at La Sabana University, Bogota (Ethical Committee December 14, 2010, no P-004-10). Considering the ethical aspects of gene diagnosis and gene therapy targeting IGF-I, IGF-I expresses tumors namely lung cancer and epidermis treated (Trojan et al., 2016).
2011
In 2007 and 2008, a man (Timothy Ray Brown) recovered from HIV with recurrent haematopoietic stem cell transplantation (see also allogenic stem cell transplant, allogeneous bone marrow transplant, allotransplantation) with a double delta-32 mutation that inactivated CCR5 receptors. This drug was accepted by the medical community in 2011. It needs a complete ablation of the existing bone marrow, which is very disabling.
In August two of the three subjects from the pilot study were confirmed to have recovered from chronic lymphocytic leukemia (CLL). Therapy uses genetically modified T cells to attack cells that express CD19 protein to fight disease. In 2013, researchers announced that 26 of 59 patients had achieved complete remission and original patients remained tumor-free.
Human plasmid HGF DNA therapy from cardiomyocytes is being examined as a potential treatment for coronary artery disease as well as treatment for damage that occurs to the heart after myocardial infarction.
In 2011 Neovasculgen was registered in Russia as the first gene therapy drug in its class for the treatment of peripheral arterial disease, including critical limb ischemia; it provides gene encoding for VEGF. Neovasculogen is a plasmid encoding CMV promoter and 165 VEGF amino acid form.
2012
The FDA approved Phase 1 clinical trials of major thalassemia patients in the US for 10 participants in July. This research is expected to continue until 2015.
In July 2012, the European Medicines Agency recommended approval of gene therapy therapy for the first time in Europe or the United States. This treatment uses Alipogene tiparvovec (Glybera) to compensate for lipoprotein lipase deficiency, which can cause severe pancreatitis. This recommendation is supported by the European Commission in November 2012 and commercial launch begins at the end of 2014. Alipogene tiparvovec is expected to cost approximately $ 1.6 million per treatment in 2012, revised to $ 1 million by 2015, making it the world's most expensive drug on time. In 2016, only one person is treated with drugs.
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 injected with treatment involving genetically engineered T cells to target NY-ESO-1 and LAGE-1 proteins. , which is present only in myeloma cancer cells.
2013
In March, researchers reported that three of the five adult subjects with acute lymphocytic leukemia (ALL) had remission for five months to two years after being treated with genetically modified T cells that attacked cells with CD19 genes on the surface, all B - cell, cancer or not. The researchers believe that the patient's immune system will make normal T-cells and B-cells after several months. They are also given bone marrow. One patient recurred and died and one died of a blood clot unrelated to the disease.
After encouraging Phase 1 trials, in April, the researchers announced that they started Phase 2 clinical trials (called CUPID2 and SERCA-LVAD) in 250 patients at several hospitals to combat heart disease. This therapy is designed to increase serCA2 levels, protein in the heart muscle, improve muscle function. The FDA provides this a Breakthrough Therapy Setting to speed up the trial and approval process. In 2016 it was reported that no improvements were found from the CUPID 2 experiment.
In July, researchers reported promising results for six children with two severe hereditary diseases having been treated with partially disabled lentiviruses to replace the damaged gene and after 7-32 months. Three of the children have metachromatic leukodystrophy, which causes children to miss cognitive and motor skills. Other children have Wiskott-Aldrich syndrome, which makes them open to infections, autoimmune diseases, and cancers. Follow-up testing with gene therapy in six other children with Wiskott-Aldrich syndrome was also reported to be promising.
In October, researchers reported that two children born with adenosine deaminase of severe combined immunodeficiency disease (ADA-SCID) had been treated with genetically engineered stem cells 18 months earlier and that their immune system showed signs of full recovery. Three other children are making progress. By 2014, another 18 children with ADA-SCID are cured with gene therapy. The ADA-SCID children do not have a functioning immune system and are sometimes known as "bubble children."
Also in October researchers reported that they had treated six people with hemophilia in early 2011 using adeno-related viruses. More than two years later all six produce clotting factors.
2014
In January, researchers reported that six chloroideremic patients had been treated with adeno-related viruses with a copy of REP1. Over a period of six months to two years everything has improved his eyesight. By 2016, 32 patients have been treated with positive results and researchers hope treatment will last long. Choroideremia is a genetic eye disease that is passed on without approved treatment, leading to loss of vision.
In March, researchers reported that 12 HIV patients had been treated since 2009 in trials with a genetically engineered virus with a rare mutation (CCR5 deficiency) known to protect against HIV with promising results.
Clinical trials of gene therapy for sickle cell disease begin in 2014. There is a need for high-quality randomized controlled trials that assess the risks and benefits involved with gene therapy for people with sickle cell disease.
2015
In February, LentiGlobin BB305, gene therapy therapy undergoing clinical trials for the treatment of beta thalassemia acquired the FDA's "breakthrough" status after some patients were able to undo the blood transfusions normally required to treat the disease.
In March, researchers presented recombinant genes that encode antibodies that neutralize extensively to apes infected with HIV simian; Monkey cells produce antibodies, which cleanse them from HIV. This technique is named immunoprophylaxis by gene transfer (IGT). Animal testing for antibodies against ebola, malaria, influenza, and hepatitis is ongoing.
In March, scientists, including the inventor of CRISPR, Jennifer Doudna, urged a worldwide moratorium on germline gene therapy, writes "scientists should avoid even trying, in weak jurisdictions, germline genome modification for clinical applications in humans" until full implications " discussed among scientific and governmental organizations ".
In October, researchers announced that they had treated a baby girl, Layla Richards, with experimental treatment using a genetically engineered T-cell donor using TALEN to attack cancer cells. One year after treatment, he is still free of his cancer (a very aggressive form of acute lymphoblastic leukemia [ALL]). Children with ALL who are very aggressive usually have a very poor prognosis and Layla disease has been considered a terminal before treatment.
In December, scientists from major world academies called for an inherited moratorium on human genomic edits, including those associated with CRISPR-Cas9 technology but basic research including embryo gene editing should continue.
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In April the Committee on Drug Products for Human Use of the European Drug Agency approved a gene therapy therapy called Strimvelis and the European Commission approved it in June. It treats children born with adenosine deaminase deficiency and who have no functioning immune system. This is the second approved gene therapy therapy in Europe.
In October, Chinese scientists reported that they have begun trials to genetically modify the T cells from 10 adult patients with lung cancer and instruct re-modified T cells into their bodies to attack cancer cells. T-cells have PD-1 proteins (which stop or slow the immune response) removed using CRISPR-Cas9.
A Cochrane systematic review in 2016 that looked at data from four trials on topical gene transmembranous fibrosis topical (CFTR) gene therapy therapy did not support its clinical use as a mist inhaled into the lungs to treat patients with cystic fibrosis with lung infections. One of the four experiments found weak evidence that liposomal-based CFTR gene transfer therapy may cause small respiratory repair for people with CF. This weak evidence is not sufficient to make clinical recommendations for routine CFTR gene therapy.
2017
In February Kite Pharma announced the results of clinical trials of CAR-T cells in about a hundred people with advanced non-Hodgkin lymphoma.
In March, French scientists reported a clinical study of gene therapy to treat sickle cell disease.
In August, the FDA approved tisagenlecleucel for acute lymphoblastic leukemia. Tisagenlecleucel is a lift cell transfer therapy for acute lymphoblastic leukemia of B cells; T cells from a person with cancer are removed, genetically engineered to make specific T-cell receptors (chimeric T-cell receptor, or "CAR-T") reacting to cancer, and given back to the person. T cells are engineered to target a protein called CD19 common to B cells. This is the first form of gene therapy approved in the United States. In October, a similar therapy called axicabtagene ciloleucel was approved for non-Hodgkin's lymphoma.
In December, the results used an adeno-related virus with blood clotting factor VIII to treat nine hemophilia A patients published. Six of the seven patients in the high-dose regimen increased blood clotting rates VIII to normal levels. Low and moderate dose regimens have no effect on patient's blood clotting rate.
In December, the FDA approved Luxturna, the first in vivo gene therapy, for the treatment of blindness due to congenital amaurosis Leber. The price of this treatment is 850,000 US dollars for both eyes. CRISPR gene editing technology has also been used in mice to treat deafness due to DFNA36 mutations, which also affect humans.
Speculative use
Specific uses for gene therapy include:
Fertility
Genetic Therapy Techniques have the potential to provide alternative treatments for those with infertility. Recently, successful experiments on mice have proved that fertility can be recovered using the gene therapy method, CRISPR. Spermatogenic stem cells from other organisms are transplanted into the testes of infertile male rats. Stem cells restore spermatogenesis and fertility.
Gene doping
Athletes may adopt gene therapy technology to improve their performance. Gene doping is not known to occur, but some gene therapy may have such effects. Kayser et al. argues that gene doping can equalize the playing field if all athletes receive equal access. Critics claim that any therapeutic intervention for non-therapeutic/enhancement purposes jeopardizes the basics of medical and sporting ethics.
Human genetic engineering
Genetic engineering can be used to cure diseases, but also to alter physical appearance, metabolism, and even improve physical abilities and mental abilities such as memory and intelligence. The ethical claims about germline engineering include the belief that each fetus has the right to remain genetically unmodified, that parents have the right to genetically modify their offspring, and that every child has the right to be born free from preventable diseases. For parents, genetic engineering can be seen as another child improvement technique for diet, exercise, education, training, cosmetics, and plastic surgery. Other theorists claim that moral issues are limiting but do not prohibit germline engineering.
Possible setting schemes include complete restrictions, provisions for everyone, or professional self-regulation. The American Medical Association's Council on Ethical and Judicial Affairs states that "genetic interventions to improve traits should be considered permissible only in very limited situations: (1) clear and meaningful benefits to the fetus or child; (2) no trade-offs with other characteristics or properties, and (3) equal access to genetic technology, regardless of income or other socioeconomic characteristics. "
Like the early history of biotechnology in 1990, there are scientists who are opposed to modifying human germline using these new tools, and such concerns continue as technology advances. With the emergence of new techniques like CRISPR, in March 2015 a group of scientists urged a worldwide moratorium on the clinical use of gene editing technology to edit human genes in a heritable manner. In April 2015, the researchers sparked controversy when they reported the results of basic research to edit the DNA of human embryos that can not live using CRISPR. A committee of the National Academy of Sciences of America and the National Academy of Medicine provides eligible support for editing the human genome by 2017 after answers have been found for safety and efficiency issues "but only for serious conditions under strict supervision."
Rule
Regulations that include genetic modification are part of general guidelines on biomedical research involving humans. No international treaties are legally binding in this area, but there are recommendations for national legislation of various bodies.
The Helsinki Declaration (Ethical Principles for Medical Research Involving Human Subjects) was amended by the General Assembly of the World Medical Association in 2008. This document provides principles that doctors and researchers should consider when engaging humans as research subjects. The statement on Gene Therapy Research initiated by the Human Genome Organization (HUGO) in 2001 provides the legal basis for all countries. The HUGO document emphasizes human freedom and compliance with human rights, and offers recommendations for somatic gene therapy, including the importance of recognizing public concerns about such research.
United States
There is no federal law that outlines protocols or restrictions on human genetic engineering. This subject is governed by overlapping regulations of local and federal agencies, including the Department of Health and Human Services, the FDA and the NIH Recombinant DNA Advisory Committee. Researchers seeking federal funds for newly investigated drug applications, (usually the case for somatic human genetic engineering), must adhere to international and federal guidelines for the protection of human subjects.
NIH serves as a major gene therapy regulator for federal government-funded research. Private funded research is recommended to follow this rule. NIH provides funding for research that develops or improves genetic engineering techniques and to evaluate ethics and quality in current research. The NIH maintains a mandatory registry of human genetic engineering research protocols that includes all federally funded projects.
The NIH advisory committee issued a set of gene manipulation guidelines. These guidelines address laboratory safety as well as human test subjects and various types of experiments involving genetic alterations. Some special sections relate to human genetic engineering, including Part III-C-1. This section describes the necessary review process and other aspects when seeking consent to initiate clinical research involving genetic transfer to human patients. Protocols for clinical trials of gene therapy should be approved by the NIH Recombinant Advisory DNA Committee prior to initiation of clinical trials; this is different from other types of clinical trials.
Like other types of drugs, the FDA regulates the quality and safety of gene therapy products and monitors how these products are used clinically. The therapeutic changes of the human genome are under the same regulatory requirements as other medical treatments. Research involving human subjects, such as clinical trials, should be reviewed and approved by the FDA and Institutional Review Board.
Popular culture
Gene therapy is the basis for the storyline of the movie I Am Legend and the TV show Will Gene Therapy Change the Human Race? . In 1994, gene therapy was a plot element in The Erlenmeyer Flask, Final of the first season of X-Files. It is also used in Stargate as a means to enable humans to use Ancient technology.
See also
- Antisense therapy
- Bioethics
- Gene therapy for color blind
- Gene therapy for epilepsy
- Gene therapy for osteoarthritis
- Gene therapy in Parkinson's disease
- Genetic engineering
- Synthetic fatigue
- Synthetic rescue
- Therapeutic gene modulation
References
Further reading
External links
Source of the article : Wikipedia
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