salmon is a genetically modified atlantic salmon developed by aquabounty technologies. the growth hormone-regulating gene in the atlantic salmon is replaced with the growth hormone-regulating gene from the pacific chinook salmon and a promoter sequence from the ocean pout thanks to the parallel development of single-cell transcriptomics, genome editing and new stem cell models we are now entering a scientifically exciting period where functional genetics is no longer restricted to animal models but can be performed directly in human samples. single-cell gene expression analysis has resolved a transcriptional road-map of human development from which key candidate genes are being identified for functional studies. using global transcriptomics data to guide experimentation, the crispr based genome editing tool has made it feasible to disrupt or remove key genes in order to elucidate function in a human setting. targeted gene modification in plants overview of geen workflow and editing possibilities genome editing using meganuclease, zfns, and talen provides a new strategy for genetic manipulation in plants and are likely to assist in the engineering of desired plant traits by modifying endogenous genes. for instance, site-specific gene addition in major crop species can be used for 'trait stacking' whereby several desired traits are physically linked to ensure their co-segregation during the breeding processes. progress in such cases have been recently reported in arabidopsis thaliana and zea mays. in arabidopsis thaliana, using zfn-assisted gene targeting, two herbicide-resistant genes (tobacco acetolactate synthase sura and surb) were introduced to sur loci with as high as 2% transformed cells with mutations. in zea mays, disruption of the target locus was achieved by zfn-induced dsbs and the resulting nhej. zfn was also used to drive herbicide-tolerance gene expression cassette (pat) into the targeted endogenous locus ipk1 in this case. such genome modification observed in the regenerated plants has been shown to be inheritable and was transmitted to the next generation. a potentially successful example of the application of genome editing techniques in crop improvement can be found in banana, where scientists used crispr/cas9 editing to inactivate the endogenous banana streak virus in the b genome of banana (musa spp.) to overcome a major challenge in banana breeding. in addition, talen-based genome engineering has been extensively tested and optimized for use in plants. talen fusions have also been used by a u.s. food ingredient company, calyxt, to improve the quality of soybean oil products and to increase the storage potential of potatoes several optimizations need to be made in order to improve editing plant genomes using zfn-mediated targeting. there is a need for reliable design and subsequent test of the nucleases, the absence of toxicity of the nucleases, the appropriate choice of the plant tissue for targeting, the routes of induction of enzyme activity, the lack of off-target mutagenesis, and a reliable detection of mutated cases. a common delivery method for crispr/cas9 in plants is agrobacterium-based transformation. t-dna is introduced directly into the plant genome by a t4ss mechanism. cas9 and grna-based expression cassettes are turned into ti plasmids, which are transformed in agrobacterium for plant application. to improve cas9 delivery in live plants, viruses are being used more effective transgene delivery. part of a series of articles onsynthetic biology synthetic biological circuits synthetic gene database biobrick registry of standard biological parts genome editing crispr gene therapy synthetic immunology artificial cells artificial gene synthesis synthetic genomics mycoplasma laboratorium protocell xenobiology nucleic acid analogue xeno nucleic acid unnatural base pair expanded genetic code mirror life other topics hazards open synthetic biology do-it-yourself biology research gene therapy the ideal gene therapy practice is that which replaces the defective gene with a normal allele at its natural location. this is advantageous over a virally delivered gene as there is no need to include the full coding sequences and regulatory sequences when only a small proportions of the gene needs to be altered as is often the case. the expression of the partially replaced genes is also more consistent with normal cell biology than full genes that are carried by viral vectors. the first clinical use of talen-based genome editing was in the treatment of cd19+ acute lymphoblastic leukemia in an 11-month old child in 2015. modified donor t cells were engineered to attack the leukemia cells, to be resistant to alemtuzumab, and to evade detection by the host immune system after introduction. extensive research has been done in cells and animals using crispr-cas9 to attempt to correct genetic mutations which cause genetic diseases such as down syndrome, spina bifida, anencephaly, and turner and klinefelter syndromes. in february 2019, medical scientists working with sangamo therapeutics, headquartered in richmond, california, announced the first ever "in body" human gene editing therapy to permanently alter dna - in a patient with hunter syndrome. clinical trials by sangamo involving gene editing using zinc finger nuclease (zfn) are ongoing. eradicating diseases researchers have used crispr-cas9 gene drives to modify genes associated with sterility in a. gambiae, the vector for malaria. this technique has further implications in eradicating other vector borne diseases such as yellow fever, dengue, and zika. the crispr-cas9 system can be programmed to modulate the population of any bacterial species by targeting clinical genotypes or epidemiological isolates. it can selectively enable the beneficial bacterial species over the harmful ones by eliminating pathogen, which gives it an advantage over broad-spectrum antibiotics. antiviral applications for therapies targeting human viruses such as hiv, herpes, and hepatitis b virus are under research. crispr can be used to target the virus or the host to disrupt genes encoding the virus cell-surface receptor proteins. in november 2018, he jiankui announced that he had edited two human embryos, to attempt to disable the gene for ccr5, which codes for a receptor that hiv uses to enter cells. he said that twin girls, lulu and nana, had been born a few weeks earlier. he said that the girls still carried functional copies of ccr5 along with disabled ccr5 (mosaicism) and were still vulnerable to hiv. the work was widely condemned as unethical, dangerous, and premature. in january 2019, scientists in china reported the creation of five identical cloned gene-edited monkeys, using the same cloning technique that was used with zhong zhong and hua hua – the first ever cloned monkeys - and dolly the sheep, and the same gene-editing crispr-cas9 technique allegedly used by he jiankui in creating the first ever gene-modified human babies lulu and nana. the monkey clones were made in order to study several medical diseases. in the near future the new crispr system will also be able to eradicate diseases and conditions that humans are predisposed for. with this new technology scientists will be able to take the genes of a human sperm cell and egg, and replace the genes that activate cancer or other abnormal or unwanted defects. this will take the stress off from parents worrying about having a child and not able to live a normal life. after just one generation of this process, the entire future of the human race would never have to worry about the problems of deformities or predisposed conditions. prospects and limitations in the future, an important goal of research into genome editing with engineered nucleases must be the improvement of the safety and specificity of the nucleases action. for example, improving the ability to detect off-target events can improve our ability to learn about ways of preventing them. in addition, zinc-fingers used in zfns are seldom completely specific, and some may cause a toxic reaction. however, the toxicity has been reported to be reduced by modifications done on the cleavage domain of the zfn. in addition, research by dana carroll into modifying the genome with engineered nucleases has shown the need for better understanding of the basic recombination and repair machinery of dna. in the future, a possible method to identify secondary targets would be to capture broken ends from cells expressing the zfns and to sequence the flanking dna using high-throughput sequencing. because of the ease of use and cost-efficiency of crispr, extensive research is currently being done on it. there are now more publications on crispr than zfn and talen despite how recent the discovery of crispr is. both crispr and talen are favored to be the choices to be implemented in large-scale productions due to their precision and efficiency. genome editing occurs also as a natural process without artificial genetic engineering. the agents that are competent to edit genetic codes are viruses or subviral rna-agents. although geen has higher efficiency than many other methods in reverse genetics, it is still not highly efficient; in many cases less than half of the treated populations obtain the desired changes. for example, when one is planning to use the cell's nhej to create a mutation, the cell's hdr systems will also be at work correcting the dsb with lower mutational rates. traditionally, mice have been the most common choice for researchers as a host of a disease model. crispr can help bridge the gap between this model and human clinical trials by creating transgenic disease models in larger animals such as pigs, dogs, and non-human primates. using the crispr-cas9 system, the programmed cas9 protein and the sgrna can be directly introduced into fertilized zygotes to achieve the desired gene modifications when creating transgenic models in rodents. this allows bypassing of the usual cell targeting stage in generating transgenic lines, and as a result, it reduces generation time by 90%. one potential that crispr brings with its effectiveness is the application of xenotransplantation. in previous research trials, crispr demonstrated the ability to target and eliminate endogenous retroviruses, which reduces the risk of transmitting diseases and reduces immune barriers. eliminating these problems improves donor organ function, which brings this application closer to a reality. in plants, genome editing is seen as a viable solution to the conservation of biodiversity. gene drive are a potential tool to alter the reproductive rate of invasive species, although there are significant associated risks. human enhancement many transhumanists see genome editing as a potential tool for human enhancement. australian biologist and professor of genetics david andrew sinclair notes that "the new technologies with genome editing will allow it to be used on individuals (...) to have (...) healthier children" – designer babies. according to a september 2016 report by the nuffield council on bioethics in the future it may be possible to enhance people with genes from other organisms or wholly synthetic genes to for example improve night vision and sense of smell. george church has compiled a list of potential genetic modifications for possibly advantageous traits such as less need for sleep, cognition-related changes that protect against alzheimer's disease, disease resistances and enhanced learning abilities along with some of the associated studies and potential negative effects. the american national academy of sciences and national academy of medicine issued a report in february 2017 giving qualified support to human genome editing. they recommended that clinical trials for genome editing might one day be permitted once answers have been found to safety and efficiency problems "but only for serious conditions under stringent oversight." risks in the 2016 worldwide threat assessment of the us intelligence community statement united states director of national intelligence, james r. clapper, named genome editing as a potential weapon of mass destruction, stating that genome editing conducted by countries with regulatory or ethical standards "different from western countries" probably increases the risk of the creation of harmful biological agents or products. according to the statement the broad distribution, low cost, and accelerated pace of development of this technology, its deliberate or unintentional misuse might lead to far-reaching economic and national security implications. for instance technologies such as crispr could be used to make "killer mosquitoes" that cause plagues that wipe out staple crops. according to a september 2016 report by the nuffield council on bioethics, the simplicity and low cost of tools to edit the genetic code will allow amateurs – or "biohackers" – to perform their own experiments, posing a potential risk from the release of genetically modified bugs. the review also found that the risks and benefits of modifying a person's genome – and having those changes pass on to future generations – are so complex that they demand urgent ethical scrutiny. such modifications might have unintended consequences which could harm not only