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
11th Jun 2020
The African Academy of Sciences and the Royal Society, supported by the UK’s Global Challenges Research Fund, recently announced the second group of recipients of the Future Leaders African Independent Research (FLAIR) fellowship. This is awarded to outstanding early-career African scientists whose research focuses on the needs of the continent.
Prof Visagie, Associate Professor at FABI, said that this is the funding he needs “to really expand and establish my research in the agricultural space”. His work is on fungi that produce mycotoxins, one of the biggest threats to African food security.
Mycotoxin contamination of food and feed pose serious threats to human and animal health in Africa, and often leads to death. According to the Food and Agricultural Organisation, 25% of crops are contaminated with fungi and mycotoxins. This leaves a high percentage of Africans, mostly from the poorest communities, and animals at high risk. Prof Visagie’s project aims to expand, document and disseminate our understanding of the diversity of mycotoxigenic fungi and mycotoxins in food and feed across South Africa.
Dr Muema is a postdoctoral fellow in the division of Microbiology in the Department of Biochemistry, Genetics and Microbiology at FABI. “As an early-career soil scientist, I see the FLAIR fellowship as a golden opportunity to establish myself, and contribute towards Africa’s food security and sustainable development,” she said. “The enablement to also include master’s students in my project will assist me in growing my career as I contribute to human capital development.”
Chickpeas not only provide nutrition but also use passenger bacteria, rhizobia, to lock nitrogen into soils, which are weathered and infertile in parts of South Africa. Dr Muema aims to identify local species of rhizobia to better understand their interaction with chickpeas, leading eventually to enhanced crop production and soil fertility. The aim of this project is to identify the diversity of native soil rhizobia that are compatible with chickpeas in different agro-ecological zones in South Africa.
Dr Gudrun Dittrich-Schröder is a postdoctoral fellow at FABI and the Department of Zoology and Entomology. She will lead investigations into the potential of CRISPR/Cas9 gene editing tools to manage invasive insect pests in agriculture and forestry. This fellowship allows her to work on cutting-edge research that addresses challenges on the continent.
The agricultural and forestry sectors are critical for future food security, are drivers of the economy and are critically linked to jobs. But pests and diseases are the biggest threats to these sectors. Current control measures cannot keep pace with the increase in pests and diseases –CRISPR/Cas9 gene editing provides a revolutionary method to control pest species. Specific areas in the genome of an insect can be targeted using CRISPR/Cas9 and by using gene drive, may promote the inheritance, and prevalence as a result, of this edited gene in pest populations. Dr Dittrich-Schröder will be using insect species from forestry and agriculture to develop and apply these tools.
“These are three outstanding young researchers,” said Prof Bernard Slippers, Director of FABI. “We are delighted with the awards and are very proud of them. I have no doubt that the fellowships will provide a significant boost to the next phase of their careers. The fellowships are not only very prestigious, but also generous in terms of the support, networks and training they offer. We are passionate about the mentorship and development of young researchers in FABI and will do everything we can to support them.”
Story by: Elsabé Brits for the University of Pretoria
8th Jun 2020
The African Centre for Gene Technologies (ACGT) together with the University of Pretoria’s Centre for Bioinformatics and Computational Biology (CBCB) and the CISCO Networking Academy, have been hosting the annual Linux for Life Scientists Workshops for three straight years now. This year’s course was facilitated fully online; a completely different format from that of previous years due to the current COVID-19 situation.
Advancements in sequencing platforms and the amount of data generated require specialized skills and programs that generally require some knowledge of command-line. Linux is one such useful alternative operating system for data analysis and visualization. Researchers use open-source Linux to analyse the huge amounts of data they generate on multiple platforms. Linux is an alternative to expensive vendor-specific software that require periodic license renewals.
The workshop was facilitated by Mr Shaheem Sadien (CISCO Networking Academy) and Professor Fourie Joubert (University of Pretoria). The Linux course facilitated over five webinars spread out over 2 weeks in May 2020. The first webinar served as an introduction to Linux and the rest of the webinars that followed covered navigation, essential commands, resources, clusters and queuing. The workshop participants were representative of all ACGT partner institutions (ARC, CSIR, UJ, UP and Wits), as well as the National Institute for Communicable Diseases (NICD), Tshwane University of Technology (TUT), University of Cape Town (UCT) and University of the Western Cape (UWC).
The ACGT wishes to thank Mr Molati Nonyane, Ms Itseng Malao, Mr Shaheem Sadien and Prof Fourie Joubert for course content and organization. The ACGT is looking to host another iteration of this course in 2020. Kindly contact our Liaison Scientist, Mr Molati Nonyane () in this regard. The ACGT plans to continue with these kinds capacity building efforts to improve the skills level of South African scientists, especially in the field of bioinformatics and data analysis.
29th May 2020
Most people who contract the dengue virus, a mosquito-borne RNA virus, experience mild symptoms or none at all. In some cases, it can cause a severe illness known as hemorrhagic fever, with bleeding, abnormal blood clotting, and leaky blood vessels that can sometimes lead to a precipitous drop in blood pressure and circulatory collapse. Curiously, in the 1960s, US army scientists in Thailand noticed this life-threatening condition occurred most frequently in two populations: first-time infected babies born to mothers who were immune to dengue, and children who had once experienced a mild or asymptomatic infection, and later contracted the virus a second time. A scary scenario began to crystalize: a second infection was sometimes worse than the first.
A series of studies in cells, animals, and people eventually gave rise to a possible explanation: antibodies created during a first-time infection could, under very specific circumstances, end up enhancing the disease rather than protecting against subsequent infections. Researchers called this “antibody-dependent enhancement,” or ADE.
ADE is one form of immune enhancement, a poorly understood group of phenomena occurring when components of our immune system that usually protect against viral infections somehow end up backfiring. It’s a concern in situations when people are continuously re-infected with particular pathogens, and with vaccines that work by injecting snippets of virus to mimic a first infection. Some immunizations, such as those against respiratory syncytial virus (RSV), have been observed in the past to make disease worse when vaccinated individuals contract the virus.
As far as researchers know, such cases are exceedingly rare across viruses. For SARS-CoV-2, it’s unclear if any forms of immune enhancement could play a role in infections or vaccines under development, but there is no evidence so far.
“[It’s just] a theoretical risk, but people are being extremely careful to make sure that this risk is not becoming a reality,” notes Paul-Henri Lambert, an immunologist and vaccinologist retired from the University of Geneva who now advises the university’s center of vaccinology and consults for a multinational collaborative project of researchers on safety evaluations of vaccine candidates. “With COVID-19, we have a disease which in eighty percent of people is selectively mild. So what you would not like is to give a vaccine that would not protect well and in a certain percentage of people make the disease worse.”
No evidence yet for antibody-dependent enhancement in COVID-19
Dengue remains the best-studied and one of the very few solid examples of ADE. It’s thought to occur in communities where there are multiple viral strains of dengue circulating. While antibodies against one dengue strain will typically reliably protect against that strain, things can go awry when the antibodies encounter a different strain of dengue. Instead of neutralizing the virus—that is, binding to and blocking a protein the pathogen needs to enter host cells—the antibodies only bind to the virus without neutralizing it.
That can become a problem when immune cells, such as macrophages, dock onto the tail ends of antibodies using specialized receptors known as Fc receptors—which they often do to clear up antibody-virus debris. Because dengue viruses can use Fc receptors to infect cells, if the antibodies aren’t disabling the pathogen, they actually end up helping the virus enter macrophages to infect the cells, Trojan horse–style, explains Dennis Burton, a microbiologist at the Scripps Research Institute in California. This amplifies viral replication, potentially pushing the immune system into over-drive and paving the way for severe disease. “That’s the hallmark of ADE, basically . . . you make infection easier, you infect more cells, you get worse disease.”
But there are still many questions surrounding ADE and its mechanism. It’s not entirely clear, for instance, if the antibodies are the sole effectors of ADE, or if other parts of the immune system also play a role. Nor is it certain whether it’s strictly the non-neutralizing characteristic of the antibodies that matters most—it could also be that neutralizing antibodies could also allow viruses to infect macrophages if they’re not numerous enough to block all key proteins across a virus’s surface.
“It might be that any antibody would enhance if you’ve got it at a dose that doesn’t work,” notes James Crowe, an immunologist at Vanderbilt University Medical Center. “This is very hard to study in humans.”
Solid evidence for ADE in natural viral infections exists only in dengue virus and some of its relatives. There are a handful of other viruses where ADE has been demonstrated in vitro—in experiments that mix macrophages or similar cells with antibodies and virus and see whether the virus is capable of infecting the cells in spite of the presence of antibodies, Crowe explains. Such experiments have found hints of ADE with viruses including Ebola virus, HIV, and coronaviruses such as SARS and MERS. However, it’s still a mystery to what extent this occurs in live organisms in the presence of a functioning immune system. “The immune system typically modulates things to your benefit. I’m not saying that ADE does not occur in the body—I’m just saying it’s difficult to bridge the results in the test tube to what happens in the body,” Crowe says.
It’s not yet clear if SARS-CoV-2 is capable of infecting macrophages. Although some scientists have reportedly spotted viral protein inside macrophages, whether it actually infects and replicates in macrophages in the body “is something investigators are trying to determine right now,” Crowe says.
Barney Graham, the deputy director of the National Institute of Allergy and Infectious Diseases’s Vaccine Research Center, which is collaborating with the company Moderna on a coronavirus vaccine, told PNAS last month that he doubts the dengue mechanism of ADE would apply to SARS-CoV-2 because the coronavirus primarily targets ACE2, not Fc, receptors, and has a very different pathogenesis compared to the dengue family. And even for the original SARS that caused an outbreak in 2003, in vitro experiments suggest that it could infect a human cell line using an Fc receptor, but the virus did not reproduce into infectious particles, Graham writes in a perspective article in Science.
It’s theoretically possible that infections caused by other coronaviruses could generate antibodies in people’s blood and cause ADE upon infection with SARS-CoV-2, but there’s little evidence for this so far, Crowe notes. And in principle, some COVID-19 patients could develop antibodies that don’t neutralize, or produce neutralizing ones at insufficient concentrations, and then develop severe symptoms once they’re infected a second time. But a handful of reported SARS-CoV-2 re-infections have been found to be due to flawed tests. And two preprints appeared last week suggesting that in US patients who received antibody-containing blood plasma transfusions from COVID-19 survivors, the treatment did not make the disease worse, supporting the argument against ADE.
ADE’s role in vaccine development
Nevertheless, ADE is a possibility that vaccine scientists are keeping a watchful eye on, in part due to experiences with other vaccines. When researchers in the 1990s tested vaccines against feline infectious peritonitis, a rare and typically fatal coronavirus disease in cats, vaccinated kittens died much sooner than unvaccinated ones after being exposed to the virus.
Such concerns have pushed some scientists to reconsider vaccine design. One explanation for why some of the early cat coronavirus vaccines caused ADE weren’t using the right vaccine targets, or the targets weren’t specific enough. This could have produced antibodies that target parts of the virus without blocking the specific site on its spike protein which it uses to infect cells—the receptor-binding domain (RBD).
This is one reason why some investigators, including microbiologist and vaccinologist Maria Bottazzi of the Baylor College of Medicine in Houston, specifically pursue the RBD as a vaccine target–to avoid the possibility of generating non-neutralizing antibodies. “If you’re just giving the immune system the only choice of making an antibody to the receptor binding domain, then you drastically limit the possibility of inducing ADE,” explains her colleague, immunologist David Corry.
Burton says vaccine tests in animal models will help researchers understand the likelihood of ADE occurring in a COVID-19 vaccine, although that won’t be conclusive proof until clinical tests in humans are conducted. Encouragingly, some recent preliminary vaccine studies found no evidence of ADE. In an April preprint, a team of researchers from the US and China showed that injecting rats with the SARS-CoV-2 RBD protein triggered a burst of neutralizing antibodies, which did not cause ADE when mixed with virus and Fc-expressing cells in vitro. In addition, even a whole inactivated virus vaccine recently tested by Chinese researchers in four macaques protected against exposure to SARS-CoV-2, and the researchers found no evidence of ADE.
As long as it’s a good vaccine with a specific target that induces a strong neutralizing antibody response, it’s unlikely we’ll see ADE, “certainly not commonly,” Crowe says. “It’s only when you have an ineffective vaccine or antibody that you might see [ADE]. And no one wants to move those [candidates] forward anyway, so that’s why I’m optimistic.”
Other mechanisms of immune enhancement in vaccines
Bottazzi says she thinks processes involving other components of the immune system may be more relevant for SARS-CoV-2 vaccine concerns than ADE. Different routes to immune enhancement came to the foreground in the 1960s during clinical trials where young children were immunized with whole-inactivated virus vaccines against respiratory syncytial virus (RSV). When the children contracted RSV naturally a few months after the vaccinations, those who were immunized got a lot sicker than those who weren’t. In fact, in one trial, 80 percent of children in the youngest cohort had to be hospitalized, and two died.
The syndrome those hospitalized kids developed is called vaccine-associated enhanced respiratory disease (ERD), and is linked with two immunological phenomena, Graham explains in the Science article. The first is a high concentration of binding antibodies that don’t neutralize the virus and result in the formation of antibody-virus complexes that get stuck in the small airways of the lungs, obstructing these spaces and driving inflammation—a mechanism considered different from ADE, Burton explains.
Researchers also unexpectedly found large numbers of certain white blood cells in the lungs of the children who died, including a proinflammatory kind of cell called an eosinophil, usually associated with allergic reactions. This raised concerns that the vaccine could have somehow primed the immune system to trigger an inappropriate cellular immune response. Normally, vaccines or viral infections trigger a particular group of T helper (Th) cells—known as Th1 cells—to mediate a cascade of reactions involving various infection-fighting immune cells.
But in several studies in animals that received a similar RSV vaccine, challenge with the RSV virus seemed to trigger certain cytokines that mobilized a very different subpopulation of T helper cells, known as Th2 cells. The lungs of inoculated mice were also packed with inflammatory cells, eosinophils in particular. Researchers hypothesized that the vaccine was inducing a response by Th2 cells, which then attracted eosinophils and somehow induced “a kind of allergic reaction,” Lambert explains.
A similar phenomenon was seen in animals that received coronavirus vaccines in the past—making researchers such as Bottazzi wary of such forms of immune enhancement. For instance, when researchers administered an inactivated SARS vaccine into mice, and then challenged them with the live virus, they also found eosinophils and other blood cells in the animals’ lungs and livers—a possible sign of Th2-type immune responses. Despite these signs of immune enhancement, that SARS vaccine did a good job in producing neutralizing responses, and vaccinated animals survived.
Bottazzi cautions against extrapolating from animal studies to humans. It’s possible cellular immune enhancement is an artifact of the animal models or the experimental system.
Of nearly 140 different COVID-19 vaccine candidates, 15 are already in human trials. “To date, I haven’t seen any clear evidence to support ADE or ERD, but it’s something you want to be aware of for sure,” Burton says. “It may be that the vaccines that are already out there—Moderna, Janssen, and so on—they may turn out to be perfectly great, we just don’t know at this point. I think it’s good to have a plan B, where if there are some problems, you can start working it out quickly what they are, and re-engineering your vaccines based on knowledge about what’s wrong.”
Story by: Katarina Zimmer for The Scientist
28th May 2020
The global demand and consumption of agricultural crops is increasing at a rapid pace. According to the 2019 Global Agricultural Productivity Report, global yield needs to increase at an average annual rate of 1.73 percent to sustainably produce food, feed, fiber and bioenergy for 10 billion people in 2050. In the US, however, agricultural productivity is struggling to keep pace with population growth, highlighting the importance of research into traditional practices as well as new ones.
In an effort to increase crop yield, scientists at Northern Arizona University’s Pathogen and Microbiome Institute (PMI) are working with Purdue University researchers to study the bacterial and fungal communities in soil to understand how microbiomes are impacting agricultural crops. They believe technological advances in microbiome science will ultimately help farmers around the world grow more food at a lower cost.
Nicholas Bokulich, a PMI assistant research professor, and Greg Caporaso, an associate professor of biological sciences and director of PMI’s Center for Applied Microbiome Science (CAMS), have been testing a long-held farming belief that phylogenetics—the study of the evolutionary relationship between organisms—should be used to define crop rotation schedules.
Please use the following link to access the rest of the article: ScienceX
Story by: Heather Tate
27th May 2020
The APOE ε4 gene variant that puts people at a greater risk of developing Alzheimer’s disease also has a link to COVID-19. According to a study published today (May 26) in The Journals of Gerontology, Series A, carrying two copies of the variant, often called APOE4, makes people twice as likely to develop a severe form of the disease, which is caused by the SARS-CoV-2 coronavirus currently spreading around the world.
David Melzer of Exeter University and colleagues used genetic and health data on volunteers in the UK Biobank to look at the role of the APOE4 variant, which affects cholesterol transport and inflammation. Of some 383,000 people of European descent included in the study, more than 9,000 carried two copies. The researchers cross-referenced this list with people who tested positive for COVID-19 between March 16 and April 26—the assumption being that most such cases were severe because testing at the time was largely limited to hospital settings. The analysis suggested that the APOE4 homozygous genotype was linked to a doubled risk of severe disease, compared with people who had two copies of another variant called ε3.
The result isn’t due to nursing home settings or to a greater likelihood of having a diagnosis of dementia, which none of the 37 people with two copies of APOE4 who tested positive for COVID-19 had. “It is pretty bulletproof—whatever associated disease we remove, the association is still there,” Melzer tells The Guardian. “So it looks as if it is the gene variant that is doing it.”
It is still possible that dementia itself is playing a roll, says David Curtis, an honorary professor at the University College London Genetics Institute, to The Guardian. Some of those 37 people who tested positive have or will develop cognitive issues, but just don’t have a diagnosis currently. “I’m afraid this study does not really convince me that the ApoE e4 allele [gene variant] is really an independent risk factor for severe Covid-19 infection. I would want to see this tested in a sample where dementia could be more confidently excluded, perhaps a younger cohort. I am sure additional data will soon emerge to illuminate this issue.”
If APOE4 is influencing the course of a SARS-CoV-2 infection, it wouldn’t be the first gene to be fingered as an important factor. Variants in the ACE2 gene that encodes the protein SARS-CoV-2 binds to on host cells, in the HLA genes, and in the genes encoding the ABO blood types have also been linked to COVID-19 susceptibility or severity in preliminary studies.
Tara Spires-Jones, neurodegeneration researcher at the University of Edinburgh who did not participate in the study, tells the publication, “It is possible that the role of ApoE in the immune system is important in the disease and future research may be able to harness this to develop effective treatments.”
Story by: Jef Akst for The Scientist
15th May 2020
An NC State researcher has developed a new way to get CRISPR/Cas9 into plant cells without inserting foreign DNA. This allows for precise genetic deletions or replacements, without inserting foreign DNA. Therefore, the end product is not a genetically modified organism, or GMO.
CRISPR/Cas9 is a tool that can be used to precisely cut and remove or replace a specific genetic sequence. The Cas9 protein serves as a pair of molecular scissors, guided to the specific genetic target by an easily swapped RNA guide. Basically, it seeks out a specific genetic sequence and, when it finds that sequence, cuts it out. Once the target DNA is snipped, it can be deleted or replaced.
The CRISPR/Cas9 system has tremendous potential for improving crops by changing their genetic code. That does not necessarily mean inserting foreign DNA, but the systems used to deliver CRISPR/Cas9 into a plant’s cells often do, which means the relevant crop is a GMO. GMOs undergo through a rigorous evaluation process and many consumers prefer non-GMO products.
Please use the following link to access the rest of the article: ScienceX
Story by: Mollie Rappe
23rd Apr 2020
Two South African entrepreneurs have developed a ground-breaking testing kit that promises to significantly speed up the process of identifying positive COVID-19 cases.
Allan Gray Orbis Foundation Fellows Daniel Ndima and Dineo Lioma have developed a testing kit that provides results in just 65 minutes, through their company CapeBio.
Testing is a pillar of any campaign against coronavirus, not only because it identifies infected individuals but because it also provides an idea of how the virus may be developing within the country. Once scientists potentially understand its spread, the government can plan resources accordingly.
This is why the qCPR kits developed by CapeBio are hailed as a massive breakthrough, with critical implications for the country’s ability to weather the current crisis
“The ability to obtain rapid test results allows us to gain a clearer picture of viral infections so that we are able to introduce interventions with greater effectiveness,” explains Daniel Ndima, CEO of CapeBio.
“This will remain important even after lockdown, as South Africa has a population of over 55 million people who will need to be monitored on an ongoing basis.”
A scientist with a special interest in structural biology, Ndima says that the development of the kits represents a spinoff of the work he has dedicated the past 12 years of his life to.
“Our kits help pathologists isolate and identify a virus’s DNA or genetic material from an infected person. This makes it possible to detect the virus accurately in a laboratory.”
As a locally manufactured product, the qCPR could mitigate the reliance on overseas imports, ensuring that testing reagents could be accessed quickly and without a wait. They are also more affordable than international products. Most importantly, CapeBio’s product makes it possible to obtain test results in just 65 minutes, compared to the usual three hours.
Collaboration for solutions
While efforts have been made to reduce the spread of the virus, Ndima points out that the impact of the crisis on our economy is just as concerning as the toll on our healthcare systems.
With this in mind, Ndima says that entrepreneurs would do well to consider their offerings and tactics, so they are better suited to a drastically changed ‘post coronavirus’ world. One of the hallmarks of this world is collaboration, he notes.
CapeBio has benefited from collaboration it with the Department of Science and Innovation’s COVID-19 response team, where experts from universities and R&D centres around the country have been given a platform to share ideas and capabilities in the search for viable solutions. But this is not the only mentorship Ndima has received – he has been guided along his entrepreneurial journey by the Allan Gray Orbis Foundation Fellowship Programme.
The Fellowship Programme is one of three programmes the Foundation offers in pursuit of creating a pipeline of responsible entrepreneurs. The Foundation provides Fellowship recipients, known as Allan Gray Candidate Fellows, funding for university studies as well as access to support and development to cultivate an entrepreneurial mindset. These programmes run throughout the academic year alongside the Candidate Fellow’s university studies.
The post-coronavirus world offers an opportunity for businesses to reimagine their offerings, believes Ndima.
“All of us need to go back to the drawing boards, rethink tactics, collaborate and rebuild, using the benefits offered by 4IR tools to create high impact businesses. This global pandemic is presenting us with serious health and economic threats, but I think it could present us with stimulated business mindsets going into the new world – so that, hopefully, we can build businesses rooted in kindness to all our people and a sense of responsibility and patriotism to our nation,” he concludes.
Story by: Tech Financials
9th Apr 2020
L. Jubair et al., “Systemic delivery of CRISPR/Cas9 targeting HPV oncogenes is effective at eliminating established tumors,” Mol Ther, 27:2091–99, 2019.
When the human papillomavirus enters a cervix, it doesn’t lyse cells or cause inflammation. While some strains can cause genital warts, in most cases the body clears the virus without much fuss. But “in an unfortunate number of people, the virus gets stuck,” says Nigel McMillan, a cancer researcher at Griffith University in Queensland, Australia. Even 15 or 20 years after infection with certain human pap-illomavirus (HPV) strains, cervical and other cancers can develop as a result.
Looking for a new way to treat these cancers, McMillan focused on two oncogenes, E6 and E7, that HPV delivers to host cells. If E6 and E7 are turned off, cancer cells will not survive—a phenomenon known as oncogene addiction. In the early 2000s, McMillan and others used short interfering RNAs (siRNAs) to reduce levels of the mRNA products of these two oncogenes. This treatment killed cancer cells in vitro, but there was no effective and commercially available way to get the siRNA to tumors in a live animal.
So in 2009, McMillan and his colleagues began working with something called stealth liposomes. Unlike regular liposomes, which are spherical phospholipid containers that researchers can use to deliver drugs into cells but which are often targeted by the immune system to be removed from the body, these liposomes are coated with a polyethylene glycol (PEG) layer that’s nontoxic and non-immunogenic. In a mouse model that had been injected with cancer cells, tumors shrank considerably when the animals were treated with siRNA-loaded stealth liposomes. But the tumors never completely disappeared.
In 2013, CRISPR-Cas9 gene editing burst onto the scientific scene, and by 2016 McMillan decided to try deploying it against the HPV oncogenes. With CRISPR, “we were actually attacking the very gene, the absolute primary cause of this cancer,” rather than its products, as siRNAs did, says McMillan. His team made guide RNAs targeting the E7 gene and put them into PEGylated liposomes along with the other components needed for CRISPR-Cas9 editing. They then injected the liposomes into the bloodstreams of mice with tumors
The PEG coating falls off within 24 hours of injection, allowing the liposome to merge with tumor cells and release the CRISPR-Cas9 system, shutting down E7. McMillan and graduate student Luqman Jubair gave some of the mice three injections, which caused the tumors’ growth to slow, but still, it didn’t stop. In a separate group of mice given seven injections, the tumors disappeared altogether. “It was like, ‘Holy moly! This is amazing,’” says McMillan. “We kept being amazed each time we did a measurement.”
McMillan says the study is the first example he knows of wiping out cancer in vivo using CRISPR. Edward Stadtmauer, a clinical oncologist and researcher at the University of Pennsylvania who was not involved in this study but recently demonstrated the safe use of CRISPR-edited cells in cancer patients, writes in an email that the work is “certainly innovative” and demonstrates “really interesting delivery of CRISPR technology to tumors in a mouse model.”
McMillan hopes to launch a clinical trial of liposomes delivered via a patch placed on the cervix, rather than intravenously, in the next couple of years, working with Kevin Morris, a gene therapy researcher at City of Hope Hospital in California who wasn’t involved in the current study. “It’s the whole package,” Morris says of McMillan’s study. “He’s shown here that you can obliterate the cancer itself.”