26th Oct 2020
The African Centre for Gene Technologies (ACGT) and Metabolomics South Africa (MSA) hosted another successful metabolomics webinar on the 14th of October 2020. This Metabolomics webinar series serves as a platform for discussions on key technologies, techniques or new data analyses that could be of relevance to the rest of the South African metabolomics community.
Professor Justin J.J. van der Hooft, an Assistant Professor at Wageningen University, facilitated a webinar on the challenges of metabolite annotation and identification in untargeted metabolomics experiments of complex mixtures, typically encountered in natural products and food research. Untargeted metabolomics approaches are now widely used, spanning various disciplines including natural products discovery and “foodomics”. This webinar focused on how recently developed tools inspired by natural language processing, facilitate metabolomics analyses.
Prof van der Hooft is currently developing computational metabolomics methodologies to decompose complex metabolite mixtures aided by natural language processing and genomic tools. His interests are in plant- and microbiome-associated metabolites and the food metabolome as prime examples; where expanded knowledge on the specialized metabolome will assist in understanding key metabolic drivers of growth and health.
Similar to previous events, this webinar proved very popular to a diverse audience. It was attended by 102 participants from across South Africa, as well as from some international research institutions. There was a great Q&A session that followed and this highlighted the need for more of these sorts of meetings. The resources for those who wish to enter the field or perform a specific metabolomics application was also highlighted.The ACGT and MSA wishes to thank Prof van der Hooft for his superb webinar and look forward to collaborative opportunities in the field.
For a recording of this webinar, or for more information and suggestions about potential advanced biotechnology-related events, please contact Mr Molati Nonyane at .
12th Oct 2020
Africa’s leading research, development and innovation organisation, the Council for Scientific and Industrial Research (CSIR), has reached a major milestone, as today, 5 October 2020, marks 75 years of its existence.
Established in 1945, the CSIR has, for seven and a half decades, dedicated its resources to improving the quality of life of South Africans through ground-breaking research, development and innovation.
The organisation’s mandate has remained the intrinsic guiding force over the years, with the focus having been refined to respond to the global and local context. A refined focus resulted in, for example, the spin out of a number of institutions and the establishment of science councils, such as the South African Bureau of Standards, National Research Foundation, National Metrology Institute of South Africa, and the Human Sciences Research Council.
Professor Thokozani Majozi, Chairperson of the CSIR Board, said the organisation has a rich heritage and strong reputation for excellence and innovation.
“The CSIR is an exceptional organisation and our unique multidisciplinary capability, and the focus on making an impact in improving the quality of lives of South Africans is our steadfast pursuit. This outstanding feat bears testimony to the relevance of the CSIR and the role that it has played in our ecosystem of innovation since 1945. It has played an important role in shaping the country’s science, engineering and technology space,” said Prof Majozi.
Testament to that is the sound track record and reputation that the organisation has built based on leading research and technological development. Some of the most impactful CSIR innovations and inventions throughout the decades include the first radar in South Africa (1945), the first microwave electronic distance measurement equipment, the tellurometer (1954), as well as the contribution of CSIR research to the invention of the lithium-ion battery in the 1980s. Today, lithium-ion batteries power our smart phones, laptop computers, electric vehicles, smart grids and even our homes.
True to its multidisciplinary nature, the CSIR’s impact has been experienced in diverse fields. In 1999, CSIR researchers developed a forecasting model to predict the outcome of the national elections, based on early voting results. The model has since been successfully used to predict the results for all the national and local government elections. In 2010, the organisation unveiled its state-of-the-art containment Level 3 laboratory for experiments involving HIV and TB pathogens. It enables researchers to conduct research and proof-of-concept studies for new HIV/Aids and TB diagnostics or therapeutics.
The CSIR 75-year anniversary comes as the world faces the biggest pandemic in a century, Covid-19. Prof Majozi said the fact that the CSIR managed to step up to the plate to support the country in its efforts to curb the spread of the virus, demonstrates its uniqueness and relevance.
“We collaborated with a number of local partners to produce local ventilators that have been rolled out nationwide to patients showing respiratory distress in the early phase of Covid-19 infection. To date, 7 000 ventilators have been completed and delivered to hospitals and clinics.”
Over 18 000 Covid-19 tests have been conducted at an upgraded CSIR Biosafety Level 3 laboratory in a bid to boost the country’s testing capacity, in partnership with the National Health Laboratory Service. Work is underway to manufacture South Africa’s own Covid-19 sample purification kits in large quantities, creating a steady local supply that will speed up testing and reduce the country’s reliance on international suppliers amid intense global demand. The work is being funded by the Department of Science and Innovation, the South African Medical Research Council and the Technology Innovation Agency.
CSIR CEO, Dr Thulani Dlamini says that the anniversary is not only for celebrating, but also engaging deeper with the CSIR’s vision, mission, values and future as a leading scientific and technology research organisation.
“More than ever, our country needs technological innovation for socioeconomic development, which is the only way to improve the lives of the people of South Africa. We have sharpened our focus to achieve this – we have developed a new strategy to specifically address industrial development, along with our aim of supporting a capable state.”
“Our new strategy will create a science council that plays a more visible role in industrial development, underpinned by a strong scientific and innovation capability. The strategy focuses on getting our scientists, engineers and technicians to work more closely with private sector companies in their innovation efforts, and it is upheld by the four pillars of growth, sustainability, impact and relevance”, says Dlamini.
Dlamini adds, “As part of the celebrations, we will host our 7th Biennial CSIR Conference on 11 and 12 November. Not only will we be sharing some of our exciting and impactful work, but we will also debate and discuss some of the challenges that technological innovation can help address with industry and government stakeholders. The virtual event will comprise a series of online events, including webinars, virtual tours, demonstrations and exhibitions.”
Story by:CSIR Strategic Communication unit
8th Oct 2020
The gene-editing technique CRISPR earned the 2020 Nobel Prize in chemistry. Recognition of this amazing breakthrough technology is well deserved.
But each Nobel Prize can be awarded to no more than three people, and that’s where this year’s prize gets really interesting.
Editing letters in the book of life
CRISPR is a powerful gene-editing tool that has taken molecular biology from the typewriter to the word processor age. One could say it’s like Microsoft Word for the book of life. CRISPR allows a researcher to find not just a gene, but a very specific part of a gene and change it, delete it or add a completely foreign gene. Genetic modifications that used to take sophisticated biological laboratories years to do are now done in days and at significantly less cost.
The CRISPR story begins in 1987, when molecular biologist Yoshizumi Ishino and his co-workers discovered a strange palindromic stretch of DNA in E. coli, a commonly studied stomach bacteria. No one could imagine what purpose it served.
Nearly two decades later, at the National Center for Biotechnology Information in Bethesda, Maryland, Eugene Koonin established the odd DNA’s function as a bacterial defense system composed of two parts. The first is a stretch of DNA that acts as an album of vanquished foes. When the bacterium overcomes an enemy, it snips out a section of the defeated invaders’ genetic material and places it into the album. These genetic mug shots are separated by repetitive stretches of DNA that read the same forward or backward. These bits of DNA are called Clustered Regularly Interspaced Short Palindromic Repeats – CRISPR for short.
The second component of the bacterial defense system is a search-and-destroy weapon. Each genetic mug shot has a search-and-destroy protein associated with it called a CRISPR-associated (Cas) protein. These Cas proteins circulate inside the cell, and when they encounter a stretch of genetic material corresponding to their genetic mug shot target, they kill the invader.
It took 20 years and much research to discover and understand these proteins.
Then in 2007, Danisco, a Danish food and beverage company, confirmed Koonin’s hypothesis that CRISPR is a bacterial defense system. Today, most yogurt and cheese manufacturers include CRISPR sequences in their cultures to protect their products from common viral outbreaks. According to Rodolphe Barrangou, who conducted this research at Danisco USA: “If you’ve eaten yogurt or cheese, chances are you’ve eaten CRISPR-ized cells.”
Harnessing CRISPR’s potential
Jennifer Doudna, a biochemist with extensive experience working with RNA at the University of California, Berkeley, started working with CRISPR in 2006. At a 2011 American Society for Microbiology meeting in San Juan, Puerto Rico, she met Emmanuelle Charpentier, an associate professor at the Laboratory for Molecular Infection Medicine Sweden at Umeå, who worked on a particular CRISPR-associated protein called Cas9.
Doudna and Charpentier had complementary skills. While walking around the old town of San Juan, Charpentier convinced Doudna that Cas9 was responsible for finding the DNA sequence that corresponds to the mug shot and cutting it. Doudna was intrigued and agreed to take a closer look at the role Cas9 played.
Charpentier worked with Cas9 in Streptococcus pyogenes, the bacteria that cause strep throat and flesh-eating disease. Rather than send Doudna these dangerous bacteria, she overnighted her the DNA encoding the CRISPR-Cas9. The more Doudna studied Charpentier’s molecular scissors, the more obvious it became to her that this bacterial system could be co-opted to edit DNA. She was right, and with some tweaking, she converted CRISPR-Cas9 into a gene editing tool. Doudna noted in her memoir that CRISPR-Cas9 “was the perfect bacterial weapon: a virus-seeking missile that could strike quickly and with incredible precision.”
Doudna and her collaborators wrote up their results and submitted their manuscript to the journal Science, which fast-tracked the paper and published it days after submission. Around the same time, she filed a patent application for the CRISPR-Cas9 gene-editing system.
Meanwhile, Virginijus Siksnys, a molecular biologist at Vilnius University in Lithuania with a research background in a class of proteins that cut DNA called restriction endonucleases, also foresaw the CRISPR system’s potential. He submitted his own results to the journal Cell. The editor rejected the manuscript without sending it out for review. Siksnys, confident in his work and its importance, submitted his manuscript to the Proceedings of the National Academy of Sciences. The paper was sent in before Doudna’s paper was published, but it needed some revisions and was thus published three months after Doudna’s paper appeared.
Like Doudna and Siksnys, Feng Zhang, a professor of neuroscience at MIT, was using the CRISPR-Cas9 system to edit DNA. But while the others did all their editing in solution, Zhang was slicing and dicing DNA with CRISPR-Cas9 in human cells. In January 2013, Zhang published his own Science paper. At this time, even though Doudna had applied for a patent seven months earlier, Feng Zhang asked his employers, MIT and the Broad Institute, to file a patent on his behalf.
The Broad Institute lawyers, knowing that Doudna’s claim was pending, paid an additional fee to accelerate their patent application. It worked, and they were granted a CRISPR-Cas9 patent before Doudna was eventually awarded hers. This has started a closely watched legal battle. The contest is far from over, but it seems that Doudna is winning the legal battle in the EU and Zhang in the U.S.
Politics around the prize
The decision to award the Nobel Prize to Doudna and Charpentier couldn’t have been easy. By choosing these two over Feng Zhang, the Royal Swedish Academy of Sciences sent a major message. It could have awarded the prize to a third researcher, but it didn’t. Was it a statement intended for the legal system?
Fortunately, scientists using CRISPR as a molecular editor aren’t affected by the legal battles. They can get their CRISPR systems from the Addgene open-source repository. Clinical applications of CRISPR – like finding a cure for genetic diseases such as cystic fibrosis and sickle cell anemia – will most likely be affected by the legal wranglings, as that is the technology’s most commercial use.
Often, basic science research goes nowhere. Often it goes in unexpected directions. Sometimes it leads to the most excitingly splendid conclusions. CRISPR-Cas9 is one of these cases. It started with a weirdly repeating palindrome, matured via mozzarella and yogurt and finally blossomed into a contested gene-editing tool that was awarded the 2020 Nobel Prize.
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28th Sep 2020
The ACGT and MSA would like to congratulate Dr Fidele Tugizimana, the current chairman of Metabolomics South Africa (MSA), on his appointment to the board of directors for the International Metabolomics Society (IMS). Dr Tugizimana is a research scientist with the plant metabolomics research group at the University of Johannesburg. He is also a specialist scientist in the international R&D management of the Omnia (Pty) Ltd company (SA) and a scientific consultant in the L.E.A.F. Pharmaceuticals LLC (USA & Rwanda). Dr Tugizimana’s metabolomics research interests include host-pathogen interactions, immune response (at molecular level), chemometrics, bioinformatics and metabolite identification. He is an author/co-author of metabolomics papers in leading peer-reviewed scientific journals.
This appointment to the board of directors follows previous leadership involvement with the International Metabolomics Society as a secretary of the Early-career members Network (EMN) committee (2016-2017); (ii) member of the Data Standards and Strategy Tasks groups; and (iii) member of the International Organizing Committee for the International Metabolomics Conferences 2017 and 2019. The ACGT and MSA would like to congratulate its longtime partner and friend, Dr Tugizimana on his new role and we wish him all the luck.
11th Aug 2020
South Africa is on track to manufacture its own Coronavirus disease 2019 (COVID-19) sample purification kits in large quantities within six months, creating a steady local supply that will speed up testing and reduce the country’s reliance on international suppliers amid intense global demand.
The CSIR’s Dr Previn Naicker says the technology being developed by his team is open source in that it would generate pure samples from nasal and throat swabs that can be tested for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA on any platform. The work is being funded by the Department of Science and Innovation, the South African Medical Research Council and the Technology Innovation Agency.
A reliable local supply of sample purification reagents also addresses the specific problem of patient swabs becoming non-viable for testing because of the lengthy backlogs caused by a lack of reagents. Not only do such long waiting periods compromise test results for individual patients, it compromises the entire disease management process that relies on quarantine along with quick contact tracing and testing.
“There are testing facilities that are not running at full capacity because there are not enough diagnostic reagents,” Naicker says. “The project will ensure that we close that gap and reduce the turnaround time of testing.”
The CSIR is working with local partners such as ReSyn Biosciences, a spin-off company of the CSIR that will produce magnetic beads for extracting viral RNA from test samples.
Magnetic beads offer the advantage that RNA extraction can be automated. “Every step of the diagnostic process that can be automated makes for better testing,” says Naicker.
As positive cases in South Africa continue to increase at an alarming rate, Naicker says the portion of positive cases in relation to the tests conducted shows that South Africa is under-testing. Experts say the virus will be with us for a long time to come, so Naicker’s team and their local partners plan to optimise the kit within the next two months so that validation (testing on real samples), licencing and regulatory approval by the South African Health Products Regulation Authority (SAHPRA) can take place as soon as possible.
“If all goes according to plan, we will have a market-ready kit within six months,” says Naicker.
“Based on the capacity of our local partners, kits for the extraction of a minimum of 5 000 samples can be assembled per day at a certified facility, and we are in discussions with two proposed facilities thus far.” In other words, this technology could support at least an additional 10 000 COVID-19 tests per day.
“As a scientist working in the health space, to be part of the COVID-19 response is both fulfilling and exciting,” he says. “We all have a desire to make a positive societal impact.”
Story by: Council of Scientific and Industrial Research
11th Aug 2020
The CSIR can make enough enzyme for one billion chemical reactions that can be applied in COVID-19 testing, and researchers hope to begin supplying reagents for a faster, one-step test by the end of the year.
Current polymerase chain reaction (PCR) tests for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in nasal and throat swabs involve two steps.
First, the virus’s genetic material, its RNA, must be converted to DNA using an enzyme called reverse transcriptase, in a reaction called RT-PCR. Second, PCR is then used to make thousands of copies of the DNA, until there are enough of these tiny molecules to detect.
If the test detects the targeted DNA copies, there must have been viral RNA in the sample, hence the test is positive.
The CSIR has already established a highly efficient technology to produce the enzyme needed for the second step, says senior researcher Dr Lusisizwe Kwezi. “This enzyme is known as DNA Taq polymerase, and just three grams of the protein, produced in E. coli bacteria in as little as three days, is enough for a billion PCR reactions.”
This does not equate to COVID-19 tests for a billion people because, among other technical reasons, diagnostic tests must be carefully repeated several times for each patient to ensure accurate results. But it does mean that a huge amount of this important reagent is available locally and affordably.
Another benefit of the reagent mix is that it contains a special antibody that stops the Taq enzyme from working when it is not needed. This makes it more specific when it has to amplify DNA during the PCR reaction, and more robust for potential future point-of-care testing devices.
Kwezi says that earlier this month, the CSIR delivered a 3 g batch to local company CapeBio Technologies (Pty) Ltd, which has licenced and commercialised the technology. It will be rolled out to support the national testing effort as soon as CapeBio gets approval from the South African Health Products Regulation Authority (SAHPRA).
Thanks to funding just awarded through the Strategic Health Innovation Partnership – a partnership between the South African Medical Research Council and the Department of Science and Innovation (DSI) – the CSIR and CapeBio are now working to add the reverse transcriptase enzyme to the mix as well, so that the two-step COVID-19 PCR test can be done in a single step. This will reduce the turn-around time of tests.
The antibody will be produced in plants rather than in E. coli, and Kwezi says the resulting one-step kit could be ready for national roll-out within six months, pending SAHPRA approval.
He says local availability of large amounts of such affordable ‘plug-and-play’ reagents, which also allow for faster results delivered to patients, will be critical in managing the pandemic in the long-term, as we know the virus will be with us for a long time.
Important for all South Africans to note, says Kwezi, is that this key technology in the fight against the worst pandemic the world has seen in a century, began as research years ago to supply the local molecular biology market. ”Back then, little did we know how important this would one day be. This just shows how research and development can translate concepts into technology solutions to emerging challenges whilst producing export products.”
“It is Archimedes who said, ‘give me a lever long enough and a fulcrum on which to place it, and I shall move the world’,” says Kwezi. “We have the potential in South Africa to respond to this pandemic. We have the know-how, and we are grateful for funding from DSI.”
Story by: Council for Scientific and Industrial Research
28th Jul 2020
The higher education sector globally has been disrupted by the COVID-19 pandemic. Academics have been discussing various aspects of the disruptions in a series of webinars organised by the University of Cape Town. One area of particular interest is how the pandemic could affect international research collaborations. The Conversation Africa’s Nontobeko Mtshali asked panellists to share their views.
Could COVID-19 change the power dynamics between African and foreign institutions when it comes to research collaboration?
Salome Maswime: There have been many successful global research collaborations. But there’s a long history of unequal partnerships and research collaborations between African institutions and research institutions from developed countries. African researchers have often described unequal power dynamics. These have been fuelled by what can be described as a top-down approach, a sense of tokenism. There’s a sense that research agendas are driven by interests of collaborating centres instead of the needs of the communities involved.
One big change is that, prior to COVID-19, collaborators could travel to conduct research. But implementation is now dependent on the full buy-in of the local institution.
The pandemic has also compelled us to look for African solutions for Africa, and to ensure that we don’t miss out on the opportunity to be part of important discoveries like vaccines and drug treatments.
Rifat Atun: COVID-19 will likely affect the power relationship between African and foreign institutions. To date this power relationship has been hugely imbalanced. It’s been in favour of research institutions from high-income countries at the expense of African researchers and institutions.
The COVID-19 pandemic has clearly revealed that research undertaken in African countries – and subsequent policies related to COVID-19 – are critical not just for Africa but for the world. What’s also apparent is the importance of local contexts in relation to the behaviour of the epidemic and responses to different policies. This has shown how necessary it is to have locally generated research led by researchers who understand local contexts.
The speed of the epidemic has made it imperative to quickly develop local capacity in Africa to lead and undertake research – and reduce dependence.
One adverse consequence of the COVID-19 pandemic is the economic crisis that has followed. This is likely to lead to reduced research funding for health. Another adverse effect is the greater national focus on self-sufficiency. It could risk undermining international collaborations.
Kevin Marsh: It could contribute to a change that long predates the pandemic and which has been gathering pace.
Historically, we’re all aware of the imbalance in many such relationships. This reflects a structural consequence of colonialism, in terms of where money and scientific expertise and decision making were centred.
This has in fact begun to change markedly over the last few years. There are now many more researchers on the continent beginning to exercise their autonomy and leadership. The centre of gravity is changing in relation to defining African research priorities and funding.
Similarly, there are plenty of international collaborators who recognise and support these changes.
Other factors include the fact that, unlike Ebola, collaboration cannot involve a mass influx of collaborators from “outside”. Another is that there has been real synergy between continental organisations in setting priorities. These include the Africa Centres for Disease Control and Prevention, World Health Organisation Regional Office for Africa and the African Academy of Sciences.
How could things change?
Salome Maswime: This could lead to collaborations that are truly lateral with all collaborators involved from the design phase of the project to completion.
Often organisations with funding have the means to set up research sites and to employ research staff, with little buy-in and minimal engagement from the stakeholders in collaborating institutions. With virtual communication, there’s more transparency and more visibility. And no excuse for lack of representation.
The African community has also taken a keen interest in science, collaborations, equity and ethics with COVID-19. This could lead to more community engagement with research. It could also see greater effort at improving science communication. Curiosity about the safety of vaccines and drug trials, the risks in Africa and the credibility of the organisations involved are examples of how science has become a priority on the continent.
Rifat Atun: The change could be positive. It can empower African research institutions and enable the development of local research capacity that can design, implement and evaluate large research studies in Africa and beyond.
The new environment gives Africa the opportunity to lead local research and development using local capacity rather than being a “venue” for research for researchers from high-income countries who all too often take the credit for the studies. Africa must develop research and development capacity and transition to greater self-sufficiency in critical supplies of vaccines, medicines and health products.
Does COVID-19 open possibilities that didn’t exist before?
Salome Maswime: With the acceleration of virtual communication there’s been wider engagement locally and more South-South partnerships forming. Previously we’d rely on funding for meetings to engage on research projects. But more scientific groups are being formed virtually to respond to COVID-19 and local challenges.
There are also opportunities to increase research capacity and training through online education. Over the past eight weeks, hundreds of South Africans have attended live webinars run by Professor Mamokgethi Phakeng, the Vice-Chancellor of the University of Cape Town, on postgraduate research methods. This is a great example of an approach to research that inspires and empowers aspiring researchers.
After the pandemic we have an opportunity to form truly lateral partnerships driven by the needs of African communities.
Rifat Atun: There’s an opportunity to establish regional and continent-wide research networks to undertake research in Africa. There’s also the opportunity to be part of international and global studies and lead them.
Kevin Marsh: There is a sudden increase in funding – so in that sense the answer is yes. But more positively and importantly, we’re seeing that the response from the scientific community on the continent in taking leadership has been strong. So in many ways COVID-19 has revealed this rather than caused it.
Salome Maswime, Professor of Global Surgery, University of Cape Town; Kevin Marsh, Professor of Tropical Medicine, University of Oxford, and Rifat Atun, Professor of Global Health Systems, Harvard University
16th Jul 2020
The African Centre for Gene Technologies (ACGT) and Metabolomics South Africa (MSA) are always looking for ways to create more Metabolomics platforms for discussions and training. One such initiative was to start up a Metabolomics Webinar Series that will run throughout 2020. The idea is to have a webinar hosted by a local expert once a month or so to discuss a key technique or new data that could be of relevance to the rest of the South African metabolomics community.
The first webinar of the series was hosted by Dr Shayne Mason on the 9th July 2020 at 14:00. Dr Shayne Mason is from the Laboratory for Infectious Diseases in Human Metabolomics at the North-West University (NWU) Potchefstroom campus. Dr Mason is a research leader at NWU specializing in TB meningitis and biofluid analysis. Dr Mason completed not one, but two BSc degrees; one in Biochemistry and Microbiology and the other in Statistics and Applied Mathematics. He completed his PhD in 2016 as a joint degree between NWU and VU in Amsterdam in the field of nuclear magnetic resonance (NMR) metabolomics. Dr Mason has published over 20 publications in the field and assisted and/or supervised numerous postgraduate students.
Then idea for this webinar was birthed from a question. One of the issues that stood out at a previous ACGT/MSA workshop was “how does one interpret the NMR spectra to determine the metabolites?” This webinar is aimed at answering that question and more.
And Answer it did.
The webinar addressed one of the major challenges in metabolomics which is the identification of metabolites in a highly complex mixture of compounds that produce a forest of peaks in a NMR spectrum. Dr Mason gave a practical stepwise guide description of how to perform 1H-NMR metabolite profiling on multiple complex biological samples. This metabolite identification process, called metabolite profiling, involves fitting the mixture spectrum to a set of individual pure reference spectra obtained from known pure compounds. The fitting process yields not only the identity of the metabolites, but also the accurate concentration of those metabolites. The participants were given a path to successful metabolite profiling that would provide them with a table of metabolite names and their absolute or relative concentrations.
This webinar was attended by 128 participants from all over South Africa. There was a great Q&A session that followed and this highlighted the need for more of these sorts of meetings. Please look out for future communication about the next webinar and other ACGT events.
6th Jul 2020
The ability of CRISPR gene-editing technology to safely modify human embryos has been cast into doubt after several recent papers described massive disruptions to DNA in embryos subjected to editing.
Each of the three papers, published this month without peer review on the preprint server bioRxiv, intended to edit only a single gene. But results showed large-scale, unintended DNA deletions and rearrangements in the areas surrounding the targeted sequence. While past research has shown that gene editing can lead to mutations far away from the targeted region, these studies instead draw attention to more localized damage involving larger sequences of DNA that could be overlooked by traditional safety screenings, Nature reports.
These studies were intended only for research purposes, meaning the embryos were destroyed after the experiment ended. But in response to their findings, many researchers are voicing their objections to further editing. The field itself is still grappling with the fallout from the birth of twin girls as a result of highly controversial CRISPR experiments carried out by He Jiankui at the Southern University of Science and Technology in China in 2018.
“There’s no sugarcoating this,” Fyodor Urnov, a geneticist and CRISPR researcher at the University of California, Berkeley, who was not involved with the research, tells OneZero. “This is a restraining order for all genome editors to stay the living daylights away from embryo editing.”
In the first study, published June 5, researchers at the Francis Crick Institute used CRISPR to remove the POU5F1 gene—an important contributor to embryonic development and stem cell pluripotency—in 18 embryos. When they analyzed the effect of the deletion on the genome, they unexpectedly found that eight of these embryos contained additional abnormalities, four of which involved substantial DNA rearrangements and deletions of several thousand base pairs.
A second group from Columbia University attempted to modify embryos with a blindness-causing mutation in the EYS gene, the most common gene implicated in the onset of a degenerative eye condition called retinitis pigmentosa. But in addition to the expected changes, they reported on June 18 that almost half of the 23 embryos also lost large chunks of the chromosome on which EYS is located. In the most extreme cases, the chromosome disappeared entirely.
Lastly, a study published June 20 by researchers at Oregon Health & Science University similarly focused on correcting a mutation in the MYBPC3 gene that is known to cause a heart condition. While they were successful in repairing the damage in close to half of the 86 embryos—a complement to their pioneering work in 2017—the authors also reported large disruptions in the chromosome containing the gene.
Taken together, these three studies highlight the contrast between off-target effects, which happen when the CRISPR tools edit someplace unintended, and on-target edits, in which the changes are properly localized but have some unintended consequence. In each case, the on-target effects were unexpected.
“What that means is that you’re not just changing the gene you want to change, but you’re affecting so much of the DNA around the gene you’re trying to edit that you could be inadvertently affecting other genes and causing problems,” Kiran Musunuru, a cardiologist at the University of Pennsylvania who was not involved in any of the studies, tells OneZero.
These problems also show just how little is known about the ways in which the body naturally repairs molecular cuts to the genome made by CRISPR technology, Nature reports. Rather than neatly heal the newly cleaved ends of DNA subjected to editing, the mechanism can sometimes be faulty, leading to degraded or broken DNA.
Speaking to Nature, Urnov says these on-target effects warrant the attention of researchers moving forward. “This is something that all of us in the scientific community will, starting immediately, take more seriously than we already have. This is not a one-time fluke.”
Story by: Amanda Heidt, for The Scientist
15th Jun 2020
Viruses are ubiquitous pathogens that can cause severe infectious diseases in both humans and agricultural crops. As most viruses have simple genomes and encode only a few proteins, they must usurp host cell resources for propagation. Understanding what host processes are disrupted and which viral proteins are involved greatly facilitate the design of therapeutic measures for controlling viral diseases in humans and crop plants.
Recently, researchers from the Institute of Genetics and Developmental Biology (IGDB) of the Chinese Academy of Sciences discovered a plant viral protein named 17K that disrupts host cell division to promote its own propagation in infected tissues. They also linked it structurally to certain animal virus proteins.
The work was published online in Science Advances on May 13. It is the result of a decade-long collaboration between the IGDB group led by Dr. Wang Daowen and the laboratory of Dr. Zhao Yuqi at the School of Medicine of the University of Maryland.The 17K protein is conserved in a group of cereal-infecting viruses called barley yellow dwarf viruses (BYDVs). Even though BYDVs have been studied for more than 60 years, they frequently cause severe epidemics in global wheat, barley, maize and oat crops, with yellowing and dwarfing as typical results.
– Please use the following link to access the rest of the article: ScienceX