CRISPR/Cas9 technology, where is the road?
August 27, 2015 Source: Bio Valley
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];The new technology of CRISPR/Cas9 enables people to control the DNA code more accurately, which has led to innovations in the fields of genetics and cell biology. Scientists have high hopes for it, and hope to use its power to treat cancer, including cancer. The disease further unraveles the mystery that surrounds human cells.
But this gene editing technology has also caused scientists' worries. According to the US Fun Science website, some scientists are worried that this new tool will lead parents to book "design baby"? Does the use on the patient cause unpredictable dangerous consequences? Given that this technology may be misused or misused, senior scientists have written to call for the suspension of certain new research related to this technology until the corresponding ethical guidelines are developed.
Edit DNA to cure disease
Although most human diseases are caused, at least in part, by variations in our DNA, current treatments target the symptoms of these mutations rather than their genetic roots. For example, cystic fibrosis can cause the lungs to be filled with excess mucus, and the “culprit†of the disease is a single DNA mutation.
However, current methods of treating cystic fibrosis emphasize the relief or even elimination of symptoms, the main practice is to minimize the mucus in the lungs and fight the infection, rather than correct the mutation itself. This is because it is not easy to modify human DNA with 3 billion base pairs. Moreover, the first gene therapy drug "Glybera" does not involve the modification of the patient's DNA. The drug was developed by the Dutch biotechnology company UniQure and is mainly used to treat patients with lipoprotein esterase deficiency genetic disease (LPLD). Currently, the drug is in Europe. Only for the treatment of patients with digestive disorders.
The so-called gene editing technology refers to the operation of deleting and inserting DNA nucleotide sequences. In other words, gene editing technology enables people to rewrite DNA, a book of life written by deoxynucleotides, according to their own wishes. However, scientists have long been able to edit DNA through physical and chemical mutagenesis, homologous recombination, and so on. But these methods are either random in the editing position or require a lot of manpower and resources to operate. Therefore, it is always the dream of researchers to be able to edit DNA sequences easily and accurately.
In 2012, a DNA cutting technique called "CRISPR/Cas9" was born, allowing scientists to see hope. Known as "regularly spaced clustered short palindromic repeats", CRISPR is a series of clustered DNA sequences present in some bacterial genomes, derived from an acquired immune system in bacteria and archaea. The scientists found that these repeats are identical to the DNA sequences of many phage that can invade bacteria. Further studies have found that these sequences, after being transcribed into RNA, can form a complex with a protein called CRISPR-associated protein (Cas9) produced by bacteria, which guides the Cas9 protein, so this RNA is also called Guided RNA (gRNA). When the complex detects that the invading DNA and gRNA sequences are identical, the Cas9 protein is able to cleave the invading DNA for defense purposes.
The emerging genome editing tool CRISPR/Cas9 offers a shortcut compared to previously inefficient DNA editing methods. It acts like a DNA scissor, cutting out where specific RNA sequences are pointing, thus opening up the repair process of cellular DNA – either “disarming†a gene that causes the tumor to grow wild, or on a damaged gene (such as causing cysticity). Repair of fibrosis).
Although many CRISPR/Cas9 systems require the involvement of multiple proteins, in many bacterial cells, only one endonuclease, Cas9, is sufficient. Cas9 endonuclease can perform fixed-point cleavage of various invading foreign DNA molecules under the guidance of the guide RNA. Due to the excellent directivity and specificity of the Cas9 system, it has been favored by scientists.
This technology is developing rapidly. In 2014, researchers discovered a way to cure a rare liver disease in mice using CRISPR/Cas9. On March 10, 2015, in a research paper in the journal Nature Communications, scientists at the Sac Institute of Biology in the United States also found that this method can be used to remove HIV insertion genes from human immune cells. HIV has entered blood stem cells and has taken a step toward developing drugs.
In addition, scientists at Stanford University in the United States have used this technology to construct a platform for studying aging in natural short-lived African green carp. Researchers hope that these fishes will become a valuable new model for understanding, preventing and treating aging diseases, the study was published in the February 12 issue of Cell.
The technology has been successfully applied to the precise modification of the genome of human cells, zebrafish, mice and bacteria.
Lead to ethical disputes
As this technology continues to advance, the obstacles to the modification of genes within the embryo are slowly disappearing, opening the door to so-called "designing babies" with specific looks or intelligence.
Ethicists worry that allowing parents to choose the characteristics of the fetus can have very bad consequences. Moreover, because we understand the relationship between disease and genes, there are still many shortcomings. Even if we can carry out flawless genetic surgery, we don't know how specific changes in DNA will manifest themselves in a living person. Finally, editing of germ cells such as embryos may permanently introduce altered DNA into the gene pool and pass it on to future generations.
The CRISPR/Cas9 system itself also has some drawbacks. For example, after entering the cell, it may be digested at a non-target site, resulting in off-target, which may cause cancer instead of curing cancer, which is also a major failure for clinical applications. .
As the saying goes, people are not much, and technology has not escaped this fate. At the same time as an exciting study came out, the controversy over whether human embryos should be edited is constantly escalating. Some people believe that genetic editing of embryos is promising because it can eliminate destructive genetic diseases before the baby is born; others believe that such research crosses the moral bottom line: at the beginning of this year, scientists in Nature A review article was published calling for the cessation of the use of genome editing tools to transform human germ cells. They believe that the use of existing technology for genome editing of human embryos, because the transformation of germ cells can be inherited, may have unpredictable consequences for future generations, and the abuse of these technologies may cause public outrage, and then these tools are Use in the medical field.
There is no such thing. In March of this year, due to fear of possible adverse consequences, including Nobel Prize winner David? Baltimore, the famous geneticist George? Jeff, the co-developer of CRISPR technology? Scientists such as Dana, as well as experts in law, ethics, and medicine, published a review article in Science, strongly opposing the use of CRISPR genome editing techniques to modify human germ cells. They point out that the simplicity and efficiency of the CRISPR/Cas9 genome editing technology suddenly makes accurate human germ cell editing possible. They also proposed an international conference to discuss the social, legal and ethical issues of using this rapidly evolving technology.
However, they also acknowledge that the trade-off between the risk and return of the CRISPR/Cas9 technology will tend to be beneficial to human health. They wrote: "The key to the discussion is whether the transformation of the genome can cure or cure serious diseases, if so, under what circumstances."
To manage risk, they also propose standardized benchmarks to determine the frequency and severity of off-target effects and conduct appropriate risk assessments; they call on representatives from around the world, including experts in genetics, law and bioethics, and government agencies. , private groups, and the public to discuss issues of genomic transformation and develop policies.
Although it is rare to ask for a study suspension for ethical reasons, it is not an isolated case. The previous recombinant DNA technology also suffered the same fate. At the Asilomar Conference in 1975, molecular biologists discussed the issue of the moral bottom line of recombinant DNA technology, and finally reached a consensus on safety standards, signed to ensure that artificial genetically modified organisms are not allowed. Threat to the public. Several authors of the Science paper have also participated in the Achilloma conference.
The Achilloma Conference is still widely considered to be an appropriate and responsible measure that emphasizes the safety and ethics of technology and does not hinder the pace of technological advancement. The results prove that DNA recombination technology is not as dangerous as initially feared. And the available evidence suggests that we may not be so lucky on the issue of Cas9. Another important legacy of the Achilloma conference is the promotion of open discussion between experts and the public. The CRISPR/Cas9 technology may be able to draw on this.
The gap between ideal and reality
Although these people call for the suspension of certain CRISPR/Cas9 studies before the development of stringent ethical guidelines. But a month later, a report from a Chinese research team once again pushed the technology to the forefront.
In April of this year, Huang Jun, an associate professor and gene function researcher at Sun Yat-Sen University, published a paper in the journal Protein and Cell, saying that they used CRISPR/Cas9 technology to edit non-viable human embryos in an attempt to modify humans. A gene in the embryo that may cause beta-thalassemia.
The results show that the scientists' concerns are not groundless. In the experiment, this method basically killed one-fifth of the embryos, and only half of the DNA in the surviving cells changed, and even those cells whose DNA had been modified had only a small part of the disease variation. Was fixed. Huang Jun told the team that the experimental results indicate that there are obvious obstacles from gene editing to gene therapy technology. Before any clinical application is reached, there are still many problems to be studied.
Former President of the International Society for Stem Cell Research, Harvard University biologist George? Daley is also a member of the "Science" paper. He said that this is the world's first attempt to modify human embryonic genes using CRISPR/Cas9 technology. It is a milestone and a warning. The results of this study have given severe warnings to those who believe that genetic editing can completely eliminate the disease genes.
Now, there are too many fanatics and jealousies around Cas9, and it's easy to forget that this technology has been around for less than three years.
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