Cell nuclear transplant "three parents" baby technology: gene editing technology principle.

Britain's Artificial Insemination and Embryology Authority announced Thursday that it has approved the country's first application to use the "three-parent" baby technology for cell nuclear transplantation, taking a substantial step forward in the application of the controversial technology in fertility treatment.
The Department of Artificial Insemination and Embryology says a fertility treatment facility in Newcastle, England, has received a "three-parent" baby technical certification, but this is only a certification of the agency's ability to implement the treatment program, when the agency for specific patients to apply for a second phase of certification.
"three parents" technique is to replace defective mitochondrials in the mother's eggs with healthy mitochondrials from donor eggs.
depending on the surgical method used, this process can be carried out before or after fertilization of the egg, which is currently more mature in the UK.
eventually born have the donor's mitochondrial genetic material in addition to their parents' genes.
mainly to prevent newborns from developing potentially fatal mitochondrial disease.
"three-parent" baby technology is banned in the United States and other countries because of ethical disputes, in Mexico, Ukraine and other countries have not been specified.
although clinical applications are currently permitted in the UK, any application for the use of the technology will require a rigorous process of approval.
, a professor at newcastle University in Newcastle, said mitochondrial disease was a major blow to many families and the regulator's announcement was an important moment for patients.
-editing technology is thought to be used to customize the "perfect human body", but faces many ethical problems at the application level.
. Xinhua news agency said: "If a doctor told you that before a baby is born, you can use gene editing technology to "customize" their hair color, skin color, and even IQ according to your wishes - would you think that's a good idea?"Since its birth, gene editing technology has not only brought unprecedented surprises to mankind, but also caused a lot of controversy.
, how does gene editing work? How's the latest research going? What's the use of this "magic scissors"?Let's hear what Wei Wensheng, a researcher at Peking University's School of Life Sciences, and Huang Zhiwei, dean of the School of Life Sciences and Technology at Harbin University of Technology, say.
Gene Editing Is like modifying text, first identifying errors or where you want to modify them, and then using tools to insert, delete, or rewrite a paragraph of "text" to understand the principles of gene editing, first of all to understand what a gene is.
gene is a fragment of DNA (deoxyritic acid) with genetic effects that controls the characteristics of living things and supports the basic structure and properties of life.
since the discovery of DNA, scientists have been experimenting with "gene editing", such as growing more productive wheat and choosing more hairy pets... These "primitive experiments" are never stopped.
experts say gene editing is a technique specifically designed to alter the sequence of the target gene.
As with text modifications, first identify the error or where you want to modify it, and then use the tool to insert, delete, or rewrite a paragraph of "text" according to the intent of the modification.
Of course, gene editing is a similar operation of the gene sequence within the cell, and the process is more complex: first, the target gene sequence is specifically identified by a complex to avoid "injury to innocence";
if a "template" exists during the repair process, the cells will be repaired as a standard and gene editing done.
the compound must be a "scissors" with its own "navigation system", which contains DNA identification areas and DNA cutting areas.
"scissors" are crucial in gene editing, so finding better-use "scissors" has always been a major task for gene editing.
"scissors" are artificial nucleases.
the 1990s, zinc finger nucleases (ZFNs) emerged, a technique that enables DNA identification by zinc finger proteins and precision cutting by nucleases.
more than ten years of development, zinc refers to nuclease technology has been applied to fruit flies, zebrafish, rats, mice and other models of animal genetic research, successfully achieved genetic modification.
2005, it also achieved the first targeted modification of human cell genes.
However, the accuracy of zinc finger nuclease is built on a huge zinc finger expression library, from which zinc finger protein screening, time-consuming and expensive, so no large-scale application.
"scissors" is the class transcription activation factor nuclease (TALENs), which theoretically enables editing of any gene sequence, in a similar way to zinc finger nuclease technology.
although it is easier to screen and build, it is also cumbersome and may cause the body's immune response.
Wei Wensheng pointed out that although zinc refers to nuclease, transcriptional activation factor nuclease use threshold is relatively high, but in some areas such as gene therapy, there is still important value.
Why CRISPR fire CRISPR is a civilian "magic scissors", cheaper, more convenient, more accurate targeting to make gene editing really easy and easy to use, is a gene called CRISPR "scissors."
bacteria are the most widely distributed and individual organisms in nature.
like most organisms, bacteria can be infected with viruses, making them the killers of normal bacteria, phages.
in the long evolutionary process, bacteria gradually have their own response - the immune system.
the late 1980s, when researchers looked at E. coli, they found that at the end of the bacterial gene, there were some seemingly strange sequences of repetitions.
these sequences are then named as short echo repeat sequences (CRISPRs) at regular intervals in clusters.
viral infection is like a time bomb, bacteria only have a short time to deal with it before it "explodes", and CRISPR is a "bomb disposal expert."
is CRISPR "bomb-breaking"? The researchers note that these repetitive sequences are always separated by some very odd spacer, which looks odd because they are not all part of the bacteria themselves, but are small fragments "cut" from the DNA of the phage virus.
In short, bacterial cells produce CRISPR-related proteins (Cas proteins), which, after a virus invasion, bind to viral DNA, "cut" the next piece of viral DNA from above, and then transport it to the genome of bacterial cells, where they are inserted into a "spacer zone."
, bacterial cells use this interval to identify the corresponding virus and to achieve an immune response to the virus's re-invasion.
even more amazingly, the CRISPR system can also integrate some of the resulting DNA fragments into the genome, forming memories and inheriting them, thus protecting offspring's cells from viruses, like carrying a "vaccination card" of a gene with it.
" scientists quickly realized that, based on this precise targeting capability, the CRISPR/Cas9 system could be designed to be an efficient gene-editing tool, as long as the edited cell genome DNA is treated as viral or exogenetic DNA, allowing us to use RNA (RNA) to guide Cas9 proteins to modify specific points in multiple cell genomes.
," Huang zhiwei said.
In CRISPR/Cas9 technology, the implementation of gene editing requires these two tools, the wizard RNA (gRNA) and Cas9 protein, in which Cas9 protein has the function of cutting DNA fragments, allowing DNA to break double strands, which in turn induces cells to produce DNA damage repair.
gRNA binds to cas9 proteins in cells, forming a complex that "retrieves" all the DNA in the cell, locates the site corresponding to the sequence of gRNA inside it, and then connects them so that the Cas9 protein can precisely "cut" the relevant DNA, thus editing the target gene in the cell.
" for example, the CRISPR system is equivalent to a missile, gRNA is equivalent to its guide part, and protein is equivalent to its combat part.
different genes, just change the sequence of gRNA.
," Huang zhiwei said.
Compared with zinc finger nuclease and transcriptional activation factor nuclease technology, CRISPR technology is very "civilian", it has no species restrictions, low cost, easy to get started, short experimental cycle, more accurate targeting, saving a lot of time and cost.
scientists hope to use the technology to edit human genes for disease treatment, but also hope to use the technology in crop improvement.
" proves that CRISPR technology is very powerful because it rewrites the underlying password.
," Wei Wensheng said.
CRISPR/Cas9 gene editing technology was named the most important "breakthrough discovery" of 2015 by Science magazine and is considered by scientists to be the most important genetic engineering technology since the 1970s.
gene editing can not abuse this technical weapon can not "do what you want", must strictly abide by the relevant principles and standards of the CRISPR technology to bring gene editing to the "crossroads."
" is first and foremost a matter of technology itself.
In the case of CRISPR technology, although it is very useful, but the gene 'scissors' is not the sharper the better, since it can 'target', there is also the possibility of 'off-target', 'indiscriminate killing of innocents' situation can not be completely avoided.
," Wei Wensheng said.
even more worrying for scientists is that the relative lag in ethical and safety guidelines associated with the human genome, which can also be the subject of CRISPR editing, could pose a range of problems.
such as "custom babies", if human embryos are edited, some genetic diseases from parents can be eliminated and genes lacking by parents can be added.
Wei Wensheng believes that the current discussion of some technologies is still only at the theoretical level, such as customizing a "high IQ" baby, there are many genes affecting human intelligence, which genes or which genes will improve human intelligence? This knowledge is not yet available, and ethical issues do require caution.
we should pay more attention to the supervision and guidance of technology, and guide technology to the track of sound development.
To this end, the American Academy of Sciences and the American Academy of Medicine have established the Human Gene Editing Research Council, composed of 22 scholars from around the world, to conduct comprehensive research on the science, technology, ethics and regulation of human gene editing, and to officially publish its research report to the world in February this year.
report states that the technical weapon of human gene editing cannot be "doing what it wants" and must "play by the rules" and strictly adhere to relevant principles and standards.
For somtic cell gene editing, the report proposes four principles: using existing regulatory systems to manage the research and application of human soytic cell gene editing, limiting its clinical trials and treatment in the scope of diagnosis and prevention of disease and disability, evaluating safety and effectiveness from the risks and benefits of its application, and requiring extensive public consultation before application.
report also suggests that countries could develop regulations and even legislation on human gene editing in the light of the results and recommendations of the study, in the light of their national circumstances and existing laws.
The prospects for the technology itself are very good, and the next step is to keep up with the relevant laws and regulations to ensure that gene editing can better serve us within a certain framework, " said Huang Zhiwei, a director of the technology.
the use of gene editing techniques, there is a real risk.
"But on the other hand, that's why we need to know more about and master the technology - the more we know about it, the more we have a better chance of guiding it in the right direction," says Wei Wensheng.
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