Science:CRISPR gene editing technology, controversies and the future

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Source: popular science:CRISPR gene editing technology, controversy and the future

the original title: popular science: the CRISPR gene editing technology, controversy and the future editor’s note: what is CRISPR for? Scientific community.

the original title: popular science: the CRISPR gene editing technology, controversy and the future

editor’s note: what is CRISPR for? The scientific community why for its potential applications so fascinated? This technology and ancient bacterial defense system? It and how it will affect the world around us? This article is compiled from CBInsights on the original title for What Is CRISPR? Article.

imagine the future, parents can customize baby’s look, choose unborn child’s height and eye color. All qualities are available according to personal preferences Custom: the domestic Pets of the size, plant life, etc.

this sounds like dystopian science fiction, but actually this is not out of reach.

in 2012, scientists first discovered CRISPR and the CRISPR-also known as Cas9 or CRISPR-Cas9 applications surprised.

CRISPR could revolutionize our response to some of the problems, such as cancer, food shortages and organ transplantation. In a recent report, the CRISPR can even be used as a diagnostic tool. However, as with any new technology, it may also cause unexpected problems.

The changing of DNA – life’s code – will inevitably lead to a series of difficult to envision the consequences. Society and the industry if unaware of CRISPR based knowledge, it is not the application of this technology.

next, let us from its definition, applications and limitations of in-depth understanding of CRISPR.

what is CRISPR?
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CRISPR is the bacterial genetic code and the immune system one of the defining characteristics, is bacteria used to protect themselves from the virus attacks the defense system. It is also present in the paleontological community, unicellular microorganisms in the organism.

the acronym“CRISPR”on behalf of Clustered Regularly Interspaced Short Palindromic installed or support it. Essentially, it is a series of repeated DNA sequences, and the DNA that exists between“spacers”in.

In short, the bacteria use these gene sequences to“remember”the attack which every virus.

bacteria of the virus DNA to integrate into their bacterial genome. This viral DNA eventually become the CRISPR sequence of“spacers ”it. This defense system can be in the same kind of virus again launched an attack when given bacteria to protect or immunity.

is always located in the CRISPR vicinity of the gene, referred to as Cas（CRISPR associated genes.

once activated, these genes will produce special proteins, these proteins with CRISPR Co-evolution of enzymes. These Cas enzyme can act as a cutting DNA“molecular scissors”。

recap: in fact, when the virus invades a bacterium, its unique DNA will be integrated into the bacterial genome of the CRISPR sequence. This means that the next time a virus attacks, bacteria will remember it and send the RNA and the Cas to locate and destroy the virus.

although bacteria there are other Cas enzymes in the virus attack on their own will be truncated virus, but Cas9 is animal performed this task the best enzyme. Volkswagen is well known, the term CRISPR-Cas9 refers to the cutting of animals and humans, the DNA of the Cas of the enzyme species.

In order to better apply this technology, researchers added a new step: in the CRISPR-Cas9 cutting the DNA, carry a“fixed”gene a new DNA sequence can be embedded into the new interval. Alternatively, the cutting can be at the same time“knock-out”unwanted genes, for example, disease-causing genes.

for a more the image of the argument, CRISPR-Cas9 is similar to the Word in the“Find and replace”function: CRISPR-Cas9 want to find and correct the genetic data, or“words”with new material to replace it. Or, as the CRISPR pioneer Jennifer Doudna in which A Crack In Creation: Gene Editing and the Unthinkable Power to Control Evolution in a book mentioned above, CRISPR is like a Swiss��Knife, we use it in different ways, it played by the function is also different.

CRISPR research of rapid development, has gone beyond the basis of DNA editing. 2017 12 months, the Salk Institute designed a CRISPR-Cas9 system in the immature version, it is possible without editing the genome of the case to activate or deactivate a target gene. Looking to the future, this technology can solve the gene editing permanent problem.

CRISPR how to work?

The following is the help of CRISPR-Cas9 to complete its work by three key factors:

1. Guide RNA: target genes of a section of the RNA-DNA genetic cousins to. This is in the lab design.

2. CRISPR associated protein 9 out of Cas9 will not need the DNA cut by the“scissors”

3. DNA: cut the segment after the insertion of the desired DNA fragment

The following will introduce how they work.

The Guide RNA can be used as“GPS coordinates”, for the target gene fragments on the lookup you want to edit the DNA fragments. Once the positioning is successful, the Cas9 scissors will be in the DNA to produce Double-Strand breaks, and then insert the desired DNA fragment instead.

this technology is indeed a threat to the medical. But in addition, it can also change the food we eat to our is used as a fuel of chemicals, because these can also be by gene technology design.

from the Massachusetts Institute of technology and Harvard University, the Institute’s Feng Zhang, Dr. with the nursery rhyme describes the CRISPR:

Twinkle Twinkle Big Star → Twinkle Twinkle Little Star

In this process:

1. The guide RNA positioning errors or mutations: the word“Big”is.

2. The Cas9 enzyme to cut the“Big”word.

3. Insert the correct DNA fragments, i.e., the word“Little”.

CRISPR applications

every industry can use the CRISPR: it can be for human diseases to create new drugs that help farmers grow disease-resistant crops, creation of new plant and animal species, and even let the extinct species back to life.

animal studies

since the initial discovery of the CRISPR since its application field is expanding rapidly. Although still in the early stages, but the“animal model”, namely the laboratory animal has to show us how to manipulate the CRISPR technology.

mice is the study of the CRISPR therapeutic potential of the experimental object. With more than human 90%of the genes, mice are mammals in an ideal experimental object.

mice experiments showed that CRISPR can be eliminated with pseudo hypertrophic muscular dystrophy（DMD）the relevant defective gene, the inhibition of neuropathic’s disease proteins form and eliminate HIV infection.

in 2015, Chinese scientists went through the myostatin gene gene created two Super muscular Terrier. In the absence of the gene of the case, the Beagle exhibit“muscle hypertrophy”, significantly higher than without the genetic modification of dogs stronger.

other CRISPR animal testing include the plush goat for yielding cashmere and breeding hornless cows.

human studies

with the animal studies compared to the editing of human DNA CRISPR experimental development is relatively slow, mainly due to ethical and regulatory issues.

In view of change in the human genome is permanent, the FDA for CRISPR attitude is cautious. Some scientists even proposed to suspend the CRISPR test, until we get more about the technology of human potential impact of the information.

the United States and Europe

by 2018, the United States and Europe for the CRISPR human trials.

current as of 2018 2 on 13 May, the University of Pennsylvania are waiting for the FDA for a study of final approval. This study aimed to evaluate the application of the CRISPR treatment of multiple myeloma, melanoma and sarcoma patient safety.

Europe is also likely in 2018 for the first time the body CRISPR research. CRISPR Therapeutics research focuses on a technique called β-thalassemia blood disease, this disease causes the hemoglobin of the component change.

although it relates to patient participation in clinical trials is still awaiting regulatory approval, but CRISPR has been applied to living and non-living human embryo experiments.

for example, the 2017 year 8 months, by the Oregon health and Science University reproductive biologist Shoukhrat Mitalipov led a team to obtain a private sponsor, the use of CRISPR-Cas9 to identify the cause of myocardial thickening of the embryonic mutations. Mutant embryos in the laboratory the mutation rate is restored to 72% of high���Ordinary 50% of the heritability of.

some critics say, the embryo of the gene editing is unethical, even edited the embryos not used for transplantation. Currently this type of testing could not get Federal funding, are relying on private sponsorship.

China

other side of the world, the regulatory framework is completely different. Some of the hospital ethics Committee can in one day approved studies do not need to seek Federal Agency approval.

from 2015 onwards, China has been in for the CRISPR human trials against various cancers, HIV, and HPV. China is so far the only human trials of the country.

according to ClinicalTrials. Gov reports, China has 10 ongoing or upcoming for advanced cancer of the CRISPR treatment trials, such as Stage 4 stomach cancer and nasopharyngeal carcinoma. So far, it is said some of the patients with tumor shrinkage, but no official message.

while we’re on this technology Long-term side effects are not completely understood, but CRISPR has become China some have exhausted all conventional treatment options of the patient’s last option.

industries

CRISPR will affect the industry including pharmaceutical, food, agricultural and industrial biotechnology. Since the CRISPR-Cas9 gene editing system is very easy to set up and use, each of the field researchers can use this technology.

pharmaceutical and biotechnology

The Future of medicine will use CRISPR to write.

The current pharmaceutical R & D takes a long time, because of the need to ensure the safety of the drug, the need to thoroughly understand the drug’s side effects. Moreover, the current U.S. regulatory policies often lead to the development processes for up to decades.

however, the application of the CRISPR team can custom therapies to market faster, accelerate the traditional drug development process.

the Timeline of drug development. Credit: PhRMA

CRISPR cheaper and flexible, it can quickly identify a potential target gene, for efficient pre-clinical experiments. Because it can be used to“knock-out”different genes, CRISPR provides researchers with a faster and more affordable to study thousands of genes the way, easy to see which genes are regulated by a specific disease.< br>

of course, with the drug development process more simple, CRISPR provides a treatment of patients of the new method.

for example, single-gene diseases – from single gene mutations cause disease – can be carried out CRISPR experiment. These the nature of the disease for treatment to provide the exact goal: a single gene mutation.

based on the blood single-gene disorders such as β-thalassemia or sickle-cell is also CRISPR treatment of the ideal object, because these diseases can be carried out in vitro treatment called in vitro treatment of. The patient’s blood cells can be removed, using CRISPR technology to the treatment, and then put back into the body.

food and Agriculture

as early as the twenties of the twentieth century, the yogurt company Danisco it pioneered CRISPR early application, when the scientists used the earlier version of CRISPR to fight against the milk and yogurt in the main bacteria（Streptococcus thermophilus, the bacteria is always be the virus infection. At that time, the CRISPR technology is still immature.

due to the impacts of climate change, we urgently need the use of CRISPR protection of food and agricultural products from New bacteria against. For example, with the planting area became increasingly hot and dry, the cocoa cultivation is becoming increasingly difficult. This environmental change will further exacerbate the pathogen causing the damage.

In order to solve this problem, the University of California at Berkeley and the innovative genomics Institute IGI is the application of CRISPR to produce disease-resistant cocoa. Leading chocolate supplier MARS Inc. Also in support of this study.

gene editing can make planting more efficient. It can relieve the potatoes and tomatoes and other major crops to the global food shortage, but also can create a not affected by drought and other environmental impacts of the crops.

regulators of gene editing crop almost without any resistance, the USDA also did not manage this field. This is mainly because when CRISPR is applied to crops, will not bring any exogenous DNA: CRISPR only for editing the crop’s own genetic information, the selection of desirable traits.

in 2016, is transformed into the resistance to Browning of the white mushrooms to be the first by the United States Department of Agriculture approved the CRISPR editing of the organism. 2017 10 October, the agriculture firm DuPont Pioneerand the Broad Institute will cooperate with each other, the use of its CRISPR-Cas9 intellectual property for Agricultural Research.

this year 1 month, biotechnology company Yield10 Bioscience obtain CRISPR plants flax seed oil false flax approved, the hemp seed oil enhanced Omega-3 oil, for the manufacture of vegetable oil and animal feed.

these signs indicate that the new varieties of crops than previously thought faster into the market. If there is no USDA oversight of these products and other foods may be more quickly put into production.

this will affect the food we eat, because the food is edited later, it is possible to carry more nutrients or can on the grocery shelf longer time.

another area is the production of more lean cattle.

in 2017, 10 months, Beijing Chinese Academy of Sciences, the scientists used CRISPR for pork were genetically engineered so that the pig body fat decreased by 24%.

the researchers will mouse genes inserted into pig cells, so that the pig can better regulate body temperature.< br>

The application of this technology in the human food will be an area of concern.

industrial biotechnology

another less obvious in the field of industrial biotechnology. Using CRISPR to re-design microbes, the researchers can create new materials.

this and the entire society?

from the industrial point of view, this transformation and the creation of new chemical products is very important. We can change the microorganism to increase the diversity, creating new biomaterials, and the manufacture of more efficient biofuels. From the perfume of the active chemicals to an industrial detergent in the activity of chemicals that CRISPR will create new and more efficient biomaterials have a huge impact.

Jennifer Doudna of the first CRISPR Venture Company, Caribou Biosciences was founded in 2011, all walks of life to provide a non-therapeutic study, for a variety of industries to provide the CRISPR technology the major companies.

limitations

CRISPR’s potential benefits is very large, but this technique also has limitations.

a non-expected effect and all of the unknown variables are the new technology shortcomings, and new ethical issues and controversy also in the near future because the body of the test emerged.

side effects

The use of CRISPR to human therapy, safety is the biggest problem. With any new technology, as researchers do not identify CRISPR entire sphere of influence.

Off-target activity is a major problem. A single gene editing could lead to the genome of other local accidents. This may lead to abnormal tissue growth, leading to cancer. We need more accurate, more precise gene identification.

another problem is that the mosaic generation of possibilities. In CRISPR, after treatment, the patient can mix editing and not editing the cell, i.e., a“mosaic.” As cells constantly divide and replicate, some cells may be repaired, while other cells will not be repaired.

finally, the immune system complications means that these interventions and treatments may cause the patient’s immune system adverse reactions. Early research suggests that the immune system can achieve the purpose before processing a Cas enzyme, or cause adverse reactions, such as inflammation and the like. In 1999, the United States, and a patient died from a severe immune response, CRISPR experiments researchers should be more cautious.）

however, these three restrictions have the solution.

different enzymes as“molecular scissors”or more precise to mention tools can reduce Off-target activity. If the egg or sperm of the modified stem cells can be turned into the body within each cell of the cell for editing, you can also avoid the mosaic.

with the immune system problems occur, the researchers can be different of the Cas protein and the human is still not immune to the more hidden strains of bacteria separatedIn order to avoid unnecessary immune response. At the same time, can also for in vitro treatment, the scientists the patient’s blood cells come to the outside, and put them back before its treatment, it can bypass the immune system.

biological

CRISPR a potentially significant limitation is the CRISPR-Cas9 system The lack of surgical accuracy. Cas enzyme cutting of the DNA double helix the two chains, this“double Strand breaks”causing people to cut precision of the concern.

despite the current Cas9 enzyme is a“cutting”enzyme in most attention, but scientists are actively looking for their alternatives.

other options include a smaller version of Cas9, or completely different enzymes: Cpf1, because its easy to transport to the target DNA position is popular.

In addition to the use of other Cas enzymes than, for the treatment of gene transport carrier is another alternative tool. Harmless viruses may be a therapeutic gene carrying the mutation site, and the lipid nanoparticles can avoid the immune system to detect and avoid the immune response. Both options are very promising research pathways.

dispute

when technology can change the rules of life, its influence is far-reaching, it’s controversial. The following will list some information about the CRISPR major disputes.

design your own baby?

if we know that a gene’s location in where, you can use CRISPR in a variety of ways to manipulate it.

according to this logic, the pet owner can use a specific coat color and size of the design they want to the dog. More importantly, parents can also modify the control height or eye color gene to the“design”their children. If we can be separated out with the intelligence-related genes, and that a child’s IQ can also be manipulated.

although critics say this technique can only be used for therapeutic needs, but CRISPR’s rapid development does not seem to slow down, gene editing technology has been used for non-therapeutic purposes surgery.

in 2015, the Beijing genomics Institute, BGI, through the removal of growth-related genes, creating a“micro-pig”. This pig only 30 pounds, which is a pig of 100 pounds of normal body weight far. BGI initially want to about 1,600 $ each price to sell these miniature pigs, and to provide consumers with customized size and color choice. But the plans end in 2017 to stop.

although the BGI using TALENs and non-CRISPR to edit the pig’s genes, but CRISPR in the design of future pet time also raises similar concerns. This design application is likely to lead to animal and human evolution in the direction of the Permanent, leading to irreversible turning point.

make extinct animal resurrection

The last of the hairy mammoths appear in 3600 years ago. If we are able to bring these ancient creatures back to life, we should do so? What is the purpose? Whether out of curiosity or in order to effective scientific experiments in this field are controversial.

In short, the extinct species Resurrection is to make the extinct animals back to life. First we need to find extinct animals the nearest living relatives of the embryo, and the use of CRISPR-Cas9 in which the gene is inserted extinct species of DNA, such a Only extinct animals can once again roam the planet.

different scientific groups and organizations are already taking these actions. It is worth noting that The Long Now Foundation, called“rehabilitation and recovery”project aims to recreating extinct animals like the passenger Pigeonand mammoths. Broad the Institute of geneticist George teaches has been committed to this project.

Credit: Revive & Restore

mammoths for many scientists it is very attractive. Edit Asian elephant genome and insert from the old long furry mammoth organization of the gene, perhaps this may be a long-haired woolly mammoth resurrection, or made out of the ancient creatures of the hybrid version.

In this case, we also need to consider the climate factors: a��Researchers believe that the woolly mammoths to the far North of the forest has a great influence, which might restore the permafrost, and the reduction of emissions into the atmosphere of carbon.

extinct species resurrected by advocates also indicated that direct human caused many species to extinction, and therefore, we should work together to reverse this trend.

critics worry about, like manipulation of natural might bring more harm rather than positive effects, which may create a threat to human rise or now environment of the species.

genetic irreversible genetic variation

The use of CRISPR for“germline transformation”caused the scientific community concerns.

the transformation of somatic cells, such as skin, brain, muscle and heart cells will not be passed on to future generations. However, germline transformation of the modification is the egg or sperm cell gene, and therefore such a transformation will be passed on to future generations.

germ cell transformation raises the question: from a moral level, whether we can choose what we want genetic to offspring in the genes?

germline transformation of consequences is why now the researchers only use non-living human embryos for CRISPR research one of the reasons. 2017, 3 month, China for the first time in six living embryos on the CRISPR experiments. It is noteworthy that the experiment shows gene-editing success rate than the previously used non-living embryos in the experiment is higher.

although around this issue is controversial, but apparently, the transformation of germ cells benefits can stop or prevent the disease manifested as individual development. Germ cell therapy can also ensure that the patient’s body each of the cells are undergoing treatment.

even if an adult is inherently easy to get cancer of the physique, by the CRISPR editing germ cell gene, he can also heal, just like never never suffer from cancer.

bio-hackers

bio-hackers said they hope to use the CRISPR will shorten long before the time of the development process, but it sparked discussion of whether they should be regulated and the regulatory approach.

Image: DIY Bacterial Gene Engineering CRISPR Kit, Credit: The Odin

recently by the Do-It-Yourself (DIY)bio hack to initiate crowdfunding campaigns attracted numerous attention. Bio-hacking start-up Odin on its website sales DIY Bacterial CRISPR kit, with a retail price of 159 dollars. 2017, 10 months, Odin the Chief Executive Josiah Zayner in San Francisco at the synthetic biology Conference for their injection of a CRISPR transformation muscle growth genes.< br>

currently, this biological detection is still not relevant provisions, because it is self-injection, rather than other people’s experiments. However, FDA does prohibit this for therapeutic purposes self-injection of reagent sales.

CRISPR in the future

The CRISPR technology for future applications substantially with the life form itself as immeasurable. Although the current study focused on the treatment or food technology, but CRISPR-Cas9 technology as well as some less well-known but very practical application.

xenograft

xenotransplantation is another animal cell, tissue or organ transplanted to a human recipient in the body of the act.

because of the organ transplantation demand is very high, but the supply is unable to meet the demand, so a xenograft may be waiting for organ transplant patients hope.

The process is probably as follows:

1. Scientists in live pigs injection of human stem cells.

2. These human stem cells in the pig in vivo growth and differentiation into specific cell types.

3. Via Cas9“teachings”, stem cells eventually grow into some types of cells, namely the heart, liver, pancreas, etc.

2017 1 October, the headquarters is located in California the Salk Institute announced its own has manufactured A from porcine and human cells of the chimeric organism, in the scientific community caused a great sensation.

Xenotransplantation, Credit: eGenesis

scientists have previously in murine stem cells���In a xenograft: scientists first used the CRISPR-Cas9 removal in mice generated in the pancreas of the gene, and then the rat stem cells inserted into mouse embryos. In accordance with the procedures, the mice will continue to grow a rat pancreas.< br>

later, the researchers in the pig embryo inserted into a human stem cell, called induced pluripotent stem cells or iPSC it. For reasons of safety and effectiveness considerations, the study after 4 weeks stopped. The researchers did note that some of the transplanted to these porcine embryonic stem cells, are being turned into body tissues. Although the test rate of success compared to the mouse embryo experiment is much lower, but this is still one of the scientific achievements.

by George Church, a co-founder of eGenesis, is also in this field of research, the goal is for the human in the pig in vivo cultivation of human organs. 2017 8 months, the scientists of the pig embryo in more than 60 genes for a makeover, the purpose is to eliminate the human body at the time of transplantation exclusion of retroviruses.

if the researchers could come up with a Live animal in vivo cultured human cells, then they can create with the patient a matching organ. Each patient’s stem cells can grow out of by their own unique DNA composed of organs, thereby reducing the rejection and organ failure and other risks.

gene drive may lead to evolutionary confusion

a no mosquitoes in the future is also a malaria-free future, zika virus infection, the chikungunya virus, dengue fever – this term continue to emerge. Without these insects spread diseases all over the world life will not be affected by these disease threats.

CRISPR can help us reach this goal. However, from an evolutionary standpoint, a good idea might lead to disastrous consequences.

In General, each gene has 50% chance of being passed on to future generations. But the gene-driven but can be used to ensure that some genes have more genetic probability.

if the scientists through genetic editing techniques to change the genes of the drive, they can be for evolution to create an accelerated path.

Credit: E. OTWELL AND M. TELFER, ScienceNews.org

in 2016 12 months, Imperial College London, the researchers have conceived an eliminate the entire carrying malaria parasites in Mosquito populations method. If you want to implement this idea, by using the CRISPR system for editing genes and add the DNA sequence, thereby causing mosquitoes embryonic bias in genetic. As these mosquitoes develop and grow into adults, they will be with other wild mosquitoes mating, so that the entire Mosquito population will stop carrying malaria.< br>

but in the short run, such a good way will destroy the wild ecosystems of the natural balance, to change the natural evolutionary process. Through the ecosystem caused by the Domino effect cannot be predicted.

genome editing is a weapon of mass destruction for?

2016 2 months, by the Director of National Intelligence James clapper, prepared by the US Intelligence worldwide threat assessment report mentioned in“genome editing”is listed in the potential natural threats to security under the“mass destruction and proliferation of weapons”.

EcoNexus and the ETC Group and other genetic oversight organizations warning the public said that gene editing could be abused. CRISPR can become bio-terrorists a source of inspiration, they can by the design of the new pathogen to create a new generation of biological weapons. If an insect can carry and pass on the toxin, this technology may be a criminal organization use.

The U.S. Department of Defense’s Advanced Research Projects Agency DARPA has in response to these circumstances to prepare, and is developing an antidote, they also are trying to find to be able to reverse the harmful genes of the driving effect of the solution.

patent wars

since about CRISPR and its application the first paper published in 2012 since the University of California at Berkeley scientists, Jennifer Doudna and the Broad Institute’s Feng Zhang has been in competition the application of this technology patent.

in 2017, 2 August, the United States Patent and Trademark Office finally granted in the United States Patent and Trademark Office granted Feng Zhang CRISPR-Cas9 patent. However, the EPO this month, just undo a Broad one designed���Rights.

looking to the future, the CRISPR-related patent war and its impact on the field of study of the impact of the concern. With the large number of patent families the rise, the future of the CRISPR patent fight will continue to heat up.

conclusion

gene editing of the future in 100,50 or even 10 years after possible.

in the future, in plants, animals and even humans in modifying or designing gene may meet the law, it will also give the gene pool and the evolutionary process resulting in irreversible impacts.

although the above presented some ideas at present seems very far-fetched, but it is indeed very likely to occur. After all, the CRISPR is not an expensive and difficult to obtain technology. CRISPR technology can now be used, many people are using this technology. From farmers to researchers, CRISPR will our society produce an immeasurable effect.

original link:https://www.cbinsights.com/research/what-is-crispr/

compile group produced. Edit: Hao pengcheng

Published at Wed, 25 Feb 2018 10:10:21 +0000

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