Genome editing in the context of "Double-strand break"

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⭐ Core Definition: Genome editing

Genome editing, or genome engineering, or gene editing, is a type of genetic engineering in which DNA is inserted, deleted, modified or replaced in the genome of a living organism. Unlike early genetic engineering techniques that randomly insert genetic material into a host genome, genome editing targets the insertions to site-specific locations. The basic mechanism involved in genetic manipulations through programmable nucleases is the recognition of target genomic loci and binding of effector DNA-binding domain (DBD), double-strand breaks (DSBs) in target DNA by the restriction endonucleases (FokI and Cas), and the repair of DSBs through homology-directed recombination (HDR) or non-homologous end joining (NHEJ).

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Genome editing in the context of Medical ethics

Medical ethics is an applied branch of ethics which analyzes the practice of clinical medicine and related scientific research. Medical ethics is based on a set of values that professionals can refer to in the case of any confusion or conflict. These values include the respect for autonomy, non-maleficence, beneficence, and justice. Such tenets may allow doctors, care providers, and families to create a treatment plan and work towards the same common goal. These four values are not ranked in order of importance or relevance and they all encompass values pertaining to medical ethics. However, a conflict may arise leading to the need for hierarchy in an ethical system, such that some moral elements overrule others with the purpose of applying the best moral judgement to a difficult medical situation. Medical ethics is particularly relevant in decisions regarding involuntary treatment and involuntary commitment.

There are several codes of conduct. The Hippocratic Oath discusses basic principles for medical professionals. This document dates back to the fifth century BCE. Both The Declaration of Helsinki (1964) and The Nuremberg Code (1947) are two well-known and well respected documents contributing to medical ethics. Other important markings in the history of medical ethics include Roe v. Wade in 1973 and the development of hemodialysis in the 1960s. With hemodialysis now available, but a limited number of dialysis machines to treat patients, an ethical question arose on which patients to treat and which ones not to treat, and which factors to use in making such a decision. More recently, new techniques for gene editing aiming at treating, preventing, and curing diseases utilizing gene editing, are raising important moral questions about their applications in medicine and treatments as well as societal impacts on future generations.

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Genome editing in the context of Aromatic rice

Aromatic rice is one of the major types of rice. It is a medium- to long-grained rice. It is known for its nutty aroma and taste, which is caused by the chemical compound 2-acetyl-1-pyrroline. Varieties of aromatic rice include Ambemohar, Basmati, Jasmine, Radhunipagal, Sona Masuri, Texmati, Tulaipanji, Tulshimala, Wehani, Kalijira, Chinigura, Gobindobhog, Kali Mooch and wild Pecan rice. When cooked, the grains have a light and fluffy texture except for Gobindobhog rice which is sticky in texture.

Aromatic rice produces more 2-acetyl-1-pyrroline than usual due to a loss-of-function mutation in the BADH2 gene. The BADH2 mutation can be transferred by conventional breeding; it is a recessive trait. Gene editing can be used to induce a similar mutation in ordinary rice, turning them aromatic without affecting other traits.

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Genome editing in the context of Gene targeting

Gene targeting is a biotechnological tool used to change the DNA sequence of an organism (hence it is a form of genome editing). It is based on the natural DNA-repair mechanism of homology directed repair (HDR), including homologous recombination. Gene targeting can be used to make a range of sizes of DNA edits, from larger DNA edits such as inserting entire new genes into an organism, through to much smaller changes to the existing DNA such as a single base-pair change. Gene targeting relies on the presence of a repair template to introduce the user-defined edits to the DNA. The user (usually a scientist) will design the repair template to contain the desired edit, flanked by DNA sequence corresponding (homologous) to the region of DNA that the user wants to edit; hence the edit is targeted to a particular genomic region. In this way Gene Targeting is distinct from natural homology-directed repair, during which the 'natural' DNA repair template of the sister chromatid is used to repair broken DNA (the sister chromatid is the second copy of the gene). The alteration of DNA sequence in an organism can be useful in both a research context – for example to understand the biological role of a gene – and in biotechnology, for example to alter the traits of an organism (e.g. to improve crop plants).

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Genome editing in the context of Genetically modified organism

A genetically modified organism (GMO) is any organism whose genetic material has been altered using genetic engineering techniques. The exact definition of a genetically modified organism and what constitutes genetic engineering varies, with the most common being an organism altered in a way that "does not occur naturally by mating and/or natural recombination". A wide variety of organisms have been genetically modified (GM), including animals, plants, and microorganisms.

Genetic modification can include the introduction of new genes or enhancing, altering, or knocking out endogenous genes. In some genetic modifications, genes are transferred within the same species, across species (creating transgenic organisms), and even across kingdoms. Creating a genetically modified organism is a multi-step process. Genetic engineers must isolate the gene they wish to insert into the host organism and combine it with other genetic elements, including a promoter and terminator region and often a selectable marker. A number of techniques are available for inserting the isolated gene into the host genome. Recent advancements using genome editing techniques, notably CRISPR, have made the production of GMOs much simpler. Herbert Boyer and Stanley Cohen made the first genetically modified organism in 1973, a bacterium resistant to the antibiotic kanamycin. The first genetically modified animal, a mouse, was created in 1974 by Rudolf Jaenisch, and the first plant was produced in 1983. In 1994, the Flavr Savr tomato was released, the first commercialized genetically modified food. The first genetically modified animal to be commercialized was the GloFish (2003) and the first genetically modified animal to be approved for food use was the AquAdvantage salmon in 2015.

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Genome editing in the context of Emmanuelle Charpentier

Emmanuelle Marie Charpentier (French pronunciation: [emanɥɛl maʁi ʃaʁpɑ̃tje]; born 11 December 1968) is a French professor and researcher in microbiology, genetics, and biochemistry. She has served as a director at the Max Planck Institute for Infection Biology in Berlin since 2015. Three years later, she founded an independent research institute, the Max Planck Unit for the Science of Pathogens. In 2020, Charpentier and American biochemist Jennifer Doudna of the University of California, Berkeley, were awarded the Nobel Prize in Chemistry "for the development of a method for genome editing" (through CRISPR). This was the first science Nobel Prize ever won by two women only.

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Genome editing in the context of Jennifer Doudna

Jennifer Anne Doudna ForMemRS (/ˈddnə/; born February 19, 1964) is an American biochemist who has pioneered work in CRISPR gene editing, and made other fundamental contributions in biochemistry and genetics. She received the 2020 Nobel Prize in Chemistry, with Emmanuelle Charpentier, "for the development of a method for genome editing." She is the Li Ka Shing Chancellor's Chair Professor in the department of chemistry and the department of molecular and cell biology at the University of California, Berkeley. She has been an investigator with the Howard Hughes Medical Institute since 1997.

In 2012, Doudna and Emmanuelle Charpentier were the first to propose that CRISPR-Cas9 (enzymes from bacteria that control microbial immunity) could be used for programmable editing of genomes, which has been called one of the most significant discoveries in the history of biology. Since then, Doudna has been a leading figure in what is referred to as the "CRISPR revolution" for her fundamental work and leadership in developing CRISPR-mediated genome editing.

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Genome editing in the context of Transcription activator-like effector nuclease

Transcription activator-like effector nucleases (TALEN) are restriction enzymes that can be engineered to cut specific sequences of DNA. They are made by fusing a TAL effector DNA-binding domain to a DNA cleavage domain (a nuclease which cuts DNA strands). Transcription activator-like effectors (TALEs) can be engineered to bind to practically any desired DNA sequence, so when combined with a nuclease, DNA can be cut at specific locations. The restriction enzymes can be introduced into cells, for use in gene editing or for genome editing in situ, a technique known as genome editing with engineered nucleases. Alongside zinc finger nucleases and CRISPR/Cas9, TALEN is a prominent tool in the field of genome editing.

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