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Gene Drive
A gene drive is a natural process and technology of genetic engineering that propagates a particular suite of genes throughout a population by altering the probability that a specific allele will be transmitted to offspring (instead of the Mendelian 50% probability). Gene drives can arise through a variety of mechanisms. They have been proposed to provide an effective means of genetically modifying specific populations and entire species. The technique can employ adding, deleting, disrupting, or modifying genes. Proposed applications include exterminating insects that carry pathogens (notably mosquitoes that transmit malaria, dengue, and zika pathogens), controlling invasive species, or eliminating herbicide or pesticide resistance. As with any potentially powerful technique, gene drives can be misused in a variety of ways or induce unintended consequences. For example, a gene drive intended to affect only a local population might spread across an entire species. Gene drives th ...
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Gene Drive
A gene drive is a natural process and technology of genetic engineering that propagates a particular suite of genes throughout a population by altering the probability that a specific allele will be transmitted to offspring (instead of the Mendelian 50% probability). Gene drives can arise through a variety of mechanisms. They have been proposed to provide an effective means of genetically modifying specific populations and entire species. The technique can employ adding, deleting, disrupting, or modifying genes. Proposed applications include exterminating insects that carry pathogens (notably mosquitoes that transmit malaria, dengue, and zika pathogens), controlling invasive species, or eliminating herbicide or pesticide resistance. As with any potentially powerful technique, gene drives can be misused in a variety of ways or induce unintended consequences. For example, a gene drive intended to affect only a local population might spread across an entire species. Gene drives th ...
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Chromosome
A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are the histones. These proteins, aided by chaperone proteins, bind to and condense the DNA molecule to maintain its integrity. These chromosomes display a complex three-dimensional structure, which plays a significant role in transcriptional regulation. Chromosomes are normally visible under a light microscope only during the metaphase of cell division (where all chromosomes are aligned in the center of the cell in their condensed form). Before this happens, each chromosome is duplicated ( S phase), and both copies are joined by a centromere, resulting either in an X-shaped structure (pictured above), if the centromere is located equatorially, or a two-arm structure, if the centromere is located distally. The joined copies are now called si ...
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Virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's 1892 article describing a non-bacterial pathogen infecting tobacco plants and the discovery of the tobacco mosaic virus by Martinus Beijerinck in 1898,Dimmock p. 4 more than 9,000 virus species have been described in detail of the millions of types of viruses in the environment. Viruses are found in almost every ecosystem on Earth and are the most numerous type of biological entity. The study of viruses is known as virology, a subspeciality of microbiology. When infected, a host cell is often forced to rapidly produce thousands of copies of the original virus. When not inside an infected cell or in the process of infecting a cell, viruses exist in the form of independent particles, or ''virions'', consisting of (i) the genetic material, i. ...
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Bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among the first life forms to appear on Earth, and are present in most of its habitats. Bacteria inhabit soil, water, acidic hot springs, radioactive waste, and the deep biosphere of Earth's crust. Bacteria are vital in many stages of the nutrient cycle by recycling nutrients such as the fixation of nitrogen from the atmosphere. The nutrient cycle includes the decomposition of dead bodies; bacteria are responsible for the putrefaction stage in this process. In the biological communities surrounding hydrothermal vents and cold seeps, extremophile bacteria provide the nutrients needed to sustain life by converting dissolved compounds, such as hydrogen sulphide and methane, to energy. Bacteria also live in symbiotic and parasitic relationsh ...
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Cell Nucleus
The cell nucleus (pl. nuclei; from Latin or , meaning ''kernel'' or ''seed'') is a membrane-bound organelle found in eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, have no nuclei, and a few others including osteoclasts have many. The main structures making up the nucleus are the nuclear envelope, a double membrane that encloses the entire organelle and isolates its contents from the cellular cytoplasm; and the nuclear matrix, a network within the nucleus that adds mechanical support. The cell nucleus contains nearly all of the cell's genome. Nuclear DNA is often organized into multiple chromosomes – long stands of DNA dotted with various proteins, such as histones, that protect and organize the DNA. The genes within these chromosomes are structured in such a way to promote cell function. The nucleus maintains the integrity of genes and controls the activities of the cell by regulating gene expres ...
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Homology (biology)
In biology, homology is similarity due to shared ancestry between a pair of structures or genes in different taxa. A common example of homologous structures is the forelimbs of vertebrates, where the wings of bats and birds, the arms of primates, the front flippers of whales and the forelegs of four-legged vertebrates like dogs and crocodiles are all derived from the same ancestral tetrapod structure. Evolutionary biology explains homologous structures adapted to different purposes as the result of descent with modification from a common ancestor. The term was first applied to biology in a non-evolutionary context by the anatomist Richard Owen in 1843. Homology was later explained by Charles Darwin's theory of evolution in 1859, but had been observed before this, from Aristotle onwards, and it was explicitly analysed by Pierre Belon in 1555. In developmental biology, organs that developed in the embryo in the same manner and from similar origins, such as from matching p ...
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Double-strand Break
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA damage, resulting in tens of thousands of individual molecular lesions per cell per day. Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. Other lesions induce potentially harmful mutations in the cell's genome, which affect the survival of its daughter cells after it undergoes mitosis. As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. When normal repair processes fail, and when cellular apoptosis does not occur, irreparable DNA damage may occur, including double-strand breaks and DNA crosslinkages (interstrand crosslinks or ICLs). This can eventually lead to malignan ...
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Guide RNA
A guide RNA (gRNA) is a piece of RNA that functions as a guide for RNA- or DNA-targeting enzymes, with which it forms complexes. Very often these enzymes will delete, insert or otherwise alter the targeted RNA or DNA. They occur naturally, serving important functions, but can also be designed to be used for targeted editing, such as with CRISPR-Cas9 and CRISPR-Cas12. History RNA-editing Guide RNA was discovered in 1990 by B. Blum, N. Bakalara, and L. Simpson in the mitochondria of protists called Leishmania tarentolae. The guide RNA there is encoded in maxicircle DNA and contains sequences matching those within the edited regions of the mRNA. They enable the cleavage, insertion and deletion of bases. Guide RNA in Protists Trypanosomatid protists and other kinetoplastids have a novel post-transcriptional mitochondrial RNA modification process known as "RNA editing". They have a large segment of highly organized DNA segments in their mitochondria. This mitochondrial DNA is circul ...
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Cas12a
Cas12a (CRISPR associated protein 12a, previously known as Cpf1) is an RNA-guided endonuclease of that forms part of the CRISPR system in some bacteria and is used by scientists to modify DNA. It originates as part of a bacterial immune mechanism, where it serves to destroy the genetic material of viruses and thus protect the cell and colony from viral infection. Cas12a and other CRISPR associated endonucleases are unique in that their use of a guide RNA makes this action highly selective; they only cut DNA when it is adjacent to a certain sequence of nucleotides. In the organisms from which it originates, this guide RNA is a copy of a piece of the genome from a virus that previously infected the cell. It is of interest to researchers because it can be used to make highly targeted modifications of DNA or RNA, similar to the better known CRISPR/Cas9 system. Cas12a is distinguished from Cas9 by being smaller and simpler, not requiring a tracrRNA, and creating sticky rather tha ...
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Cas9
Cas9 (CRISPR associated protein 9, formerly called Cas5, Csn1, or Csx12) is a 160 kilodalton protein which plays a vital role in the immunological defense of certain bacteria against DNA viruses and plasmids, and is heavily utilized in genetic engineering applications. Its main function is to cut DNA and thereby alter a cell's genome. The CRISPR-Cas9 genome editing technique was a significant contributor to the Nobel Prize in Chemistry in 2020 being awarded to Emmanuelle Charpentier and Jennifer Doudna. More technically, Cas9 is a dual RNA-guided DNA endonuclease enzyme associated with the Clustered Regularly Interspaced Short Palindromic Repeats ( CRISPR) adaptive immune system in ''Streptococcus pyogenes''. ''S. pyogenes'' utilizes CRISPR to memorize and Cas9 to later interrogate and cleave foreign DNA, such as invading bacteriophage DNA or plasmid DNA. Cas9 performs this interrogation by unwinding foreign DNA and checking for sites complementary to the 20 nucleotide spacer ...
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Homing Endonuclease
The homing endonucleases are a collection of endonucleases encoded either as freestanding genes within introns, as fusions with host proteins, or as self-splicing inteins. They catalyze the hydrolysis of genomic DNA within the cells that synthesize them, but do so at very few, or even singular, locations. Repair of the hydrolyzed DNA by the host cell frequently results in the gene encoding the homing endonuclease having been copied into the cleavage site, hence the term 'homing' to describe the movement of these genes. Homing endonucleases can thereby transmit their genes horizontally within a host population, increasing their allele frequency at greater than Mendelian rates. Origin and mechanism Although the origin and function of homing endonucleases is still being researched, the most established hypothesis considers them as selfish genetic elements, similar to transposons, because they facilitate the perpetuation of the genetic elements that encode them independent of provid ...
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Non-homologous End Joining
Non-homologous end joining (NHEJ) is a pathway that repairs double-strand breaks in DNA. NHEJ is referred to as "non-homologous" because the break ends are directly ligated without the need for a homologous template, in contrast to homology directed repair(HDR), which requires a homologous sequence to guide repair. NHEJ is active in both non-dividing and proliferating cells, while HDR is not readily accessible in non-dividing cells. The term "non-homologous end joining" was coined in 1996 by Moore and Haber. NHEJ is typically guided by short homologous DNA sequences called microhomologies. These microhomologies are often present in single-stranded overhangs on the ends of double-strand breaks. When the overhangs are perfectly compatible, NHEJ usually repairs the break accurately. Imprecise repair leading to loss of nucleotides can also occur, but is much more common when the overhangs are not compatible. Inappropriate NHEJ can lead to translocations and telomere fusion, hallmarks ...
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