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22 February 2019

The Most Innovative Ways to Use CRISPR

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On 21 February 1953, American scientist James Watson and British scientist Francis Crick culminated their discovery of the molecular structure of DNA, in the form of a double helix. That discovery went on to revolutionise science, allowing researchers to understand how the carrier molecule of the genetic program of living organisms works. Nowadays, this has even more profound implications thanks to the gene editing technology CRISPR—clustered regularly interspaced short palindromic repeats—which allows scientists to precisely cut and alter the DNA of any cell.

Although CRISPR—also known as “molecular scissors”—has not yet cured diseases or put an end to world hunger, it is already being used in some surprising ways.

Convert pigs into organ donors

For decades, the best solution scientists have devised to reduce the list of thousands of people waiting to receive organ transplants around the world has been to use animal organs in humans. For example, the first heart transplant was performed in 1964, when the organ of a chimpanzee was implanted into a human, who died two hours after the operation.

In addition to the fact that the human body rejects foreign tissues, another risk of this alternative is the possibility that animal infections can be transmitted to the human recipients of the organs. But the company eGenesis, which was born in the laboratory of geneticist George Church of Harvard University, believes that CRISPR can solve or eliminate these obstacles.

The company eGenesis has used genetic editing to eliminate a family of viruses found in the DNA of pigs. Credit: eGenesis

Church’s team has used genetic editing to eliminate a family of viruses found in the DNA of pigs, so that these animals—whose lungs and heart are similar in size to humans—can be donors to people without the risk of contamination.

The company is also experimenting with CRISPR to modify genes related to the immune system and prevent the human body from rejecting donor organs. However, scientists warn that there are still some years to go before a clinical trial of human transplants with organs produced in genetically modified pigs can be made.

Alternatives to insulin

People with type 2 diabetes (insulin resistant) may one day have the option to replace injections with a skin graft that contains a CRISPR-modified version of a protein that helps insulin regulate blood glucose levels. Researchers at the University of Chicago are using CRISPR to alter the GLP-1 gene responsible for the coding of the hormone peptide 1, which causes the release of insulin and then helps to remove excess glucose from the blood.

Using CRISPR, scientists have verified that the GLP-1 gene could be modified so that its insulin-regulating effects have a long duration. About 80% of skin grafts that were applied in mice successfully released the hormone, which then appeared in the blood, regulating glucose levels for four months and reversing insulin resistance and weight gain in patients.

Researchers at the University of Chicago are using CRISPR to alter the GLP-1 gene. Credit: University of Chicago

Treatments in humans will take time to develop, but the good news is that scientists can now grow skin tissue very easily in the laboratory using stem cells. The prediction is that this technique can also treat diseases such as haemophilia (when the body cannot make blood clots properly).

End endemic diseases

Diseases transmitted by mosquitoes, especially malaria, kill more than 400,000 people each year around the world. To reduce that figure, some scientists propose using a technique called a gene drive. This is a genetic engineering tool designed to disseminate certain genes throughout a species, and although it is not a new idea, these gene drive are closer to becoming reality thanks to CRISPR.

In an article published in September 2018, researchers at Imperial College London showed that a gene drive carried out with CRISPR could suppress a population of Anopheles gambiae, the type of mosquito that transmits malaria in sub-Saharan Africa. The researchers used the genetic “cut and paste” to attack the Doublesex gene, responsible for female development. When the female mosquitoes inherited two copies of this modified gene, they could not bite or lay eggs.

A gene drive carried out with CRISPR could suppress a population of Anopheles gambiae. Credit: James D. Gathany

The researchers put those mosquitoes in cages and found that they were self-destructive for their species in their immediate environment: after eight generations, there were no longer normal females to reproduce and the population went extinct.

These types of experiments have not yet been carried out outside the laboratories—there is the possibility that the genetic alterations designed to impact populations could mutate and transmit advantageous traits to other generations—but this study proved that the genetic modification was transmitted almost 100% of the time, avoiding resistance.

Leaders of the African Union endorsed the investigation as an effort to fight malaria in their countries, but it could still be years before the technology is tested in nature.

Change the colour of flowers

The gene-editing tool successfully interrupted the gene responsible for the colour of the stems, leaves and petals. Source: Nature

Japanese scientists are using CRISPR to change the colour of the flower of a traditional garden plant (Ipomoea nil). The researchers programmed CRISPR to attack a specific gene, known as the DFR-B gene, and then inserted it into plant embryos.

The gene-editing tool successfully interrupted the DFR-B gene, which is responsible for the colour of the stems, leaves and petals, thus changing the characteristic violet colour of the flower to white.

Joana Oliveira

@joanaoliv

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