08 October 2020 12:43

Chemistry Emmanuelle Charpentier Nobel Prize in Chemistry

Gene-editing cows could cut greenhouse gas emissions from their farts and belches, study suggests

Editing the genetic make-up of cows could significantly reduce methane from their belches and farts which contribute to the climate crisis, according to a new report. Gene editing - making changes in the DNA sequence of living things, essentially tailoring characteristics - has developed rapidly in the past decade. On Wednesday, American biochemist Jennifer A Doudna and French microbiologist Emmanuelle Charpentier were awarded the Nobel Prize for the pioneering CRISPR gene editing method which can change the DNA of animals, plants and micro-organisms with exacting precision. A report published last month by nonpartisan science and tech think-thank the Information Technology and Innovation Foundation (ITIF) looked at how gene editing can tackle climate challenges, from optimising biofuels to improving the sustainability of fish and shrimp aquaculture and reducing methane emissions from rice paddies and cows. ITIF's report suggested that gene editing could lead to a 50 per cent improvement in agricultural productivity by 2050.

The methane that cows produce is mainly caused by microbes which live in a cow's digestive tract rather than the cattle themselves, the ITIF report notes. Gene editing and selective breeding could provide a long-term solution for those methane emissions. The results suggest that gene editing could dramatically reduce emissions from livestock and researchers are now seeking to extend the technique into sheep as well as cattle. Such is the possibilities for tackling climate change, ITIF calls on governments to increase research and development and "eliminate unscientific regulatory burdens on gene editing". Val Giddings, senior fellow at ITIF, who co-authored the report, said in a statement: "While it is impossible to predict the extent to which gene-edited solutions will contribute to climate change mitigation, it is clear there is considerable potential.

"The gene editing toolkit is so powerful, its applications so widespread, and its development so rapid that we simply cannot yet conceive all the ways in which it will be used in the coming decades." In 2018, there was outrage among the scientific community after a Chinese scientist He Jiankui announced that he had used gene editing to modify the DNA of twin girls before birth and make them resistant to HIV. Emmanuelle Charpentier at the Max Planck Institute for Infection Biology and Jennifer Doudna at the University of California, Berkeley have won the chemistry Nobel for their discovery of CRISPR, which has been described as a sort of editing software that can be used on DNA (which is anyway information, making the software analogy particularly apt). Charpentier and Doudna — this is the first time any science Nobel has been given to two women — found that a CRISPR-associated protein 9 (which is why their discovery is often referred to as CRISPR-Cas9) found naturally in bacteria could be used to cut DNA; in the case of the bacteria they studied, Cas9 was actually being used to attack an invading virus. Genome editing can prevent and treat many diseases — once we figure out how to use it safely in humans, and address the ethical concerns surrounding technologies such as CRISPR-Cas9. And along the way, researchers discovered that the CRISPR toolkit can be used as a diagnostic platform to detect pretty much anything — inexpensively and simply (the simplicity is purely from the perspective of the end user; the technology is very complex).

CRISPR AND COVID A CRISPR technology that can be almed at RNA could attack viruses in which the genetic materials in RNA (this is true of most flu-causing viruses and also Sars-CoV2, which causes the coronavirus disease) - although, right now, this is the realm of research. Indeed, a CRISPR technology that can be aimed at RNA could attack viruses in which the genetic material is RNA (this is true of most flu-causing viruses and also Sars-CoV2, which causes the coronavirus disease) — although, right now, this is in the realm of research. I wrote about CRISPR in a December 2019 essay on how the decade between 2010 and 2019 saw significant developments that would help create "machines that can think", facilitate "the colonisation of space" and extend human lifespans to 100 years, maybe more. Still, while the potential of CRISPR in combating a virus (such as the one that causes the coronavirus disease) is clear, years of research, clinical trials, and regulatory debates, lie in between. The link is Feluda, a quick and inexpensive test to diagnose Covid-19 that has been developed at Delhi's Institute of Genomics and Integrative Biology, and named after a fictional detective created by Satyajit Ray. The paper-based test is as quick as a rapid antigen test, and as accurate as the RT-PCR test.

The link is Feluda, a quick and inexpensive test to diagnose Covid-19 that has been developed at Delhi's Institute of Genomics and Integrative Biology, and named after a fictional detective created by Satyajit Ray (the detective's real name is Prodosh Chandra Mitra but everyone calls him by his nickname, Feluda). Debojyoti Chakraborty, one of the developers of Feluda (the other one is Souvik Maiti) described it best in a May interview with HT: "The CRISPR-based Feluda testing works by combining CRISPR biology and paper strip chemistry," he explained. "The Cas9 protein, a component of the CRISPR system, is barcoded to interact specifically with CoV2 sequence in a patient's genetic material. The complex of Cas9 with CoV2 is then applied to a paper strip, where, by using two lines (one control and other test), it is possible to determine if the original sample was infected with Covid-19." This is pretty much like popular strip-pregnancy tests — and much like them, when the strip shows two lines it means a positive result. Feluda, which will soon be launched in India by the Tata group, wouldn't have been possible without CRISPR, which is why the chemistry Nobel announced on Wednesday is significant. Still don't understand how CRISPR — clustered regularly interspaced short palindromic repeats — works or what it means for chemistry, medicine or human society? UC Berkeley's own Nobel Prize winner Jennifer Doudna explained the gene editing technology to the science podcast Radiolab in 2015. Just a couple of years after He Jiankui's brief burst of fame, it's hard to imagine a time when the hypothetical possibility of Crispr babies was an urgent crisis. Davies recounts how Crispr researchers pitched in to help fight the virus. Meanwhile, Doudna and Zhang both worked on Crispr-based tests that could deliver fast results at home. One of the most remarkable recent advances in biomedical research has been the development of highly targeted gene-editing methods such as CRISPR that can add, remove, or change a gene within a cell with great precision. The method is already being tested or used for the treatment of patients with sickle cell anemia and cancers such as multiple myeloma and liposarcoma, and today, its creators Emmanuelle Charpentier and Jennifer Doudna received the Nobel Prize in chemistry. While gene editing is remarkably precise in finding and altering genes, there is still no way to target treatment to specific locations in the body. The treatments tested so far involve removing blood stem cells or immune system T cells from the body to modify them, and then infusing them back into a patient to repopulate the bloodstream or reconstitute an immune response—an expensive and time-consuming process. Building on the accomplishments of Charpentier and Doudna, Tufts researchers have for the first time devised a way to directly deliver gene-editing packages efficiently across the blood brain barrier and into specific regions of the brain, into immune system cells, or to specific tissues and organs in mouse models. A team of Tufts biomedical engineers, led by associate professor Qiaobing Xu, sought to find a way to package the gene editing "kit" so it could be injected to do its work inside the body on targeted cells, rather than in a lab. They used lipid nanoparticles (LNPs)—tiny "bubbles" of lipid molecules that can envelop the editing enzymes and carry them to specific cells, tissues, or organs. Xu's team was able to modify the surface of these LNPs so they can eventually "stick" to certain cell types, fuse with their membranes, and release the gene-editing enzymes into the cells to do their work. By creating a mix of different heads, tails, and linkers, the researchers can screen— first in the lab—a wide variety of candidates for their ability to form LNPs that target specific cells. The best candidates can then be tested in mouse models, and further modified chemically to optimize targeting and delivery of the gene-editing enzymes to the same cells in the mouse. "We created a method around tailoring the delivery package for a wide range of potential therapeutics, including gene editing," said Xu. In an ingenious bit of chemical modeling, Xu and his team used a neurotransmitter at the head of some lipids to assist the particles in crossing the blood-brain barrier, which would otherwise be impermeable to molecule assemblies as large as an LNP. In a first, Xu's lab delivered an entire complex of messenger RNAs and enzymes making up the CRISPR kit into targeted areas of the brain in a living animal. Some slight modifications to the lipid linkers and tails helped create LNPs that could deliver into the brain the small molecule antifungal drug amphotericin B (for treatment of meningitis) and a DNA fragment that binds to and shuts down the gene producing the tau protein linked to Alzheimer's disease. More recently, Xu and his team have created LNPs to deliver gene-editing packages into T cells in mice. The LNPs they created fuse with T cells in the spleen or liver—where they typically reside—to deliver the gene-editing contents, which can then alter the molecular make-up and behavior of the T cell. Xu's approach to editing T cell genomes is much more targeted, efficient, and likely to be safer than methods tried so far using viruses to modify their genome. Xu and his team explored further the mechanism by which LNPs might find their way to their targets in the body.