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New research shows CRISPR turns normal body fat into energy-burning cells

By Harriet Piercy

Nov 1, 2020

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CRISPR (pronounced crisper) is a technology developed for the purpose of editing genomes, which in turn allows researchers to alter DNA (deoxyribonucleic acid) sequences and modify gene function. It has many potential applications, some of which allow scientists to correct genetic defects, treat and prevent the spread of diseases. Promises often linked to the technology have also raised many ethical concerns, understandably. How does CRISPR work, and what has recently been discovered?

How does CRISPR work?

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats Repetitive) is in fact shorthand for ‘CRISPR Cas9’, which are specialised stretches of DNA. The protein being Cas9 is an enzyme that acts like a pair of scissors (molecular scissors), which are capable of cutting certain strands of DNA, therefore modifying them.

The technology was adapted by following natural defense mechanisms of existent bacteria and archaea (which is the domain of single-celled microorganisms). Organisms such as these use CRISPR-derived RNA (ribonucleic acid, a complex compound of high molecular weight that functions in cellular protein synthesis and replaces DNA as a carrier of genetic codes in some viruses) as well as various Cas proteins such as Cas9. This allows these organisms to dodge attacks from harmful viruses or other foreign bodies that harm the good ones. They do so by literally chopping up and destroying the DNA of those unwelcome invaders.

CRISPR is powerful, and potentially ethically problematic, because of its ability to manipulate genes. In other words, it can edit for better, or for worse. One new discovery in particular may be sparking an interest in, we could argue, not only scientists, but the general public, too.

CRISPR’s new discovery

According to the World Health Organisation (WHO), about 39 per cent of men and 40 per cent of women are considered overweight in the world. It’s a problem, and that’s a fact. However, besides that, metabolic conditions that are linked to obesity could be treated in a not-so-distant future by removing fat from a person using CRISPR gene editing.

How humans burn body fat

Most fat merely stores energy, and some fat, known as brown and beige fat, burn glucose (a simple sugar and also a component of many carbohydrates) to produce heat, or burn energy. Human adults have plenty of white fat, which are the cells that are filled with lipids that make up fatty deposits, or storage. But we have much smaller reserves of these energy burning and storing brown fat cells.

Humans, or animals for that matter, typically lose brown fat as they age or put on weight (which is also caused by an increase in white fat). Studies have found that brown fat may be stimulated when we are exposed to cold temperatures, however so far, methods of building up or increasing this particular brown fat that burns energy rather than solely stores it within our bodies have not yet been found. Until possibly, now.

CRISPR modifies fat performance in mice

Principal investigator at Harvard University, Yu-Hua Tseng, and her colleagues have made the first attempt at getting around this challenge. The researchers have used the CRISPR gene-editing tool to give human white fat cells, the properties of brown fat, by targeting a gene uniquely expressed in brown fat for a protein called UCP1, which according to Tseng has the function to turn chemical energy into heat. These newly created cells, officially called human brown-like cells, have been named HUMBLE cells.

In furthering the researchers’ study to learn more about how HUMBLE cells function, Tseng and her colleagues transplanted either white fat, brown fat or HUMBLE cells into mice that were bred with a weakened immune system that would reject human tissue. The mice were then fed a high-fat diet.

Over a twelve week period, the mice that were given white fat cells gained weight while Tseng assumed that if they had been typically healthy mice, they would have shown signs of diabetes. The mice transplanted with brown or HUMBLE fat, gained significantly less weight, but also proved to be more sensitive to insulin, which suggests that they may be protected against diabetes all together.

The scientists concluded their study by writing that “This study provides a potential strategy to combat obesity and metabolic syndrome by using CRISPR-engineered HUMBLE cells combined with an autologous cell transfer-based therapy.”

Let’s just hope that, as the study evolves along with CRISPR technology, humans will learn from mistakes that they have made with previous CRISPR research studies.

New research shows CRISPR turns normal body fat into energy-burning cells


By Harriet Piercy

Nov 1, 2020

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China’s first CRISPR babies spark uproar in the international scientific community

By Yair Oded

Dec 7, 2018

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Chinese scientist He Jiankui has rattled the international scientific community last week when he announced that he has made the world’s first genetically edited babies, while speaking at an international gene editing summit in Hong Kong. What He claimed he has managed to do is use gene editing technique CRISPR, which is a set of DNA sequences used to detect and destroy DNA from viruses, in order to immunize two infants against HIV.

Not only were He’s statements regarding the success of his experiment misleading, but he acted in blunt defiance of internationally accepted scientific norms and ethics. As comments from scientists and researchers from throughout the world regarding this highly disturbing incident overflow, it is important to reflect on He’s actions in order to figure out what exactly went wrong, and whether similar cases in the future can be prevented.

In his experiment, He tested couples going into in vitro treatment and in which one of the partners had AIDS. He claimed that through genetic editing he will attempt to inoculate the embryos against the virus. The case which he regarded a success was that of two twins named Nana and Lulu, whose dad was HIV positive. Focusing on a gene called CCR5, which is used by the HIV virus as a gateway to infiltrate into the body, He sought to remove cells from the embryos, deactivate the CCR5 using CRISPR, and then re-insert them into the body.

This technique has been previously used by scientists studying the cells of patients suffering from the disease in order to create a vaccine for HIV. Yet, neither Nana and Lulu were carriers of the virus, which means that He took perfectly healthy cells out of the infants’ bodies, altered them, and injected them back in. And so not only was He attempting to cure a nonexisting medical need, but by messing with the girl’s genetic makeup He increased their risk to contract a number of other diseases, such as the West Nile. It remains unknown what the long-term effects of He’s experiment will be for Nana and Lulu, as He’s desired outcome (creating a minor alteration in their CCR5 genes) did not pan out as planned, leaving the girl with a CCR5 mutation unseen previously by scientists.

Furthermore, He’s experiment was conducted in complete contravention of international scientific consensus. Both in 2015 and 2017, the U.S. National Academies of Sciences, Engineering, and Medicine iterated that gene-editing of human embryos should not be executed hastily. In its 2015 release, the academies’ report stated that in the case of gene-editing, “there is a need for caution… rigorous oversight… maximum transparency,” as well as an “absence of reasonable alternatives.” The report finally concluded that much more research needs to be done before this technique is to be used on humans.

Alas, He didn’t adhere to any of these instructions and limitations. He did not inform The Southern University of Science and Technology, to which he belonged, about the experiment, and had lied about receiving the ethical approval of Shenzhen Harmonicare hospital. When He informed a few of his colleagues and fellow researchers about his intended experiment, the vast majority discouraged him from conducting it, claiming that such a step would be extremely unethical and irresponsible, particularly since the effect of CRISPR is still widely unknown to the scientific community and that extensive research must first be done on animals before it can be used to alter human genes. He ignored his colleagues’ pleas and went on to experiment with human beings.

Finally, He failed to properly inform his patients about what they were getting themselves into; presenting the research as an attempt to develop an HIV vaccine, He did not include in the consent form clear and understandable information about CRISPR and gene-editing, and instead drew up a contract that primarily removes any liability on his part should any unexpected or adverse side effects arise due to the experiment.

He’s whereabouts have been unknown for days, and it remains unclear whether he excused himself from the public eye or has been detained for his actions. Nevertheless, while the uproar about He’s experiment echoes throughout the international scientific community, there is no guarantee that such unscrupulous actions won’t repeat themselves in the future.

Presently, there is no international scientific body that monitors clinical trials and experiments. It is true that individual governments may get involved and crack down on wackos like He, but as seen in this case, they don’t have the resources to effectively defend the public from every scientist who decides to engage in unfavourable testing, especially since when it comes to science it becomes all the more difficult to determine where the line lies between innovative and unlawful.

China’s first CRISPR babies spark uproar in the international scientific community


By Yair Oded

Dec 7, 2018

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