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| 2005 CSIRO Report |
#17,717
The publication of a new study in the journal Nature yesterday on using CRISPR technology to create a transgenic `flu resistant' chicken has generated a lot of headlines overnight - and while this research provides an important `proof-of-concept' - GM chickens are unlikely to enter the marketplace anytime soon.
The idea of creating genetically modified chickens with a built-in resistance to the HPAI viruses has a lot of appeal, particularly since the resurgence and global spread of H5N1, which began in earnest in 2016.
But even 20 years ago the feasibility of genetically modifying chickens against avian influenza was being openly discussed (see 2005 CISRO Report), and over the years we've looked in on its progress several times, including:
Flu Resistant Poultry (Revisited)CSIRO: The Quest For Flu Resistant Poultry
There are a number of scientific, legal, and societal barriers to overcome, not the least of which is the public's acceptance of eating genetically modified food. The following report in GM Crops & Food illustrates the problem.
Analyzing public sentiment toward GMOs via social media between 2019-2021
(Excerpt)
Despite their benefits, GMOs are met with heavy criticism. Currently, 26 countries including France, Germany, Italy, Mexico, Russia, China, and India (19 of which are in the European Union (EU)) have partially or fully banned GMOs.13 Another 60 countries have significant restrictions on GMOs.14 One reason for this opposition to GMOs is because of the perceived weak agricultural benefits of GMOs compared to their potential risks.15 There is also a noted lack of trust and confidence by the public in regulatory processes behind GMOs.15
The furor we've seen over the release of genetically modified mosquitoes (see FDA On Proposed Oxitec Mosquito Trials In The Florida Keys) - magnified and propelled by social media - shows how quickly sentiment can build against anything related to GMOs.
Considering how reluctant tens of millions of people are to get vaccines, convincing them to consume GM chicken is going to be a hard sell.
In the EU, current laws require genetic engineering approval and experimental GMOs can only be kept in a genetic engineering facility, limiting the ability to conduct long-term tests at scale. As we've seen with poultry vaccines (see USDA Bans Import Of French Poultry Over HPAI Vaccine Concerns), any country that approved GM chickens would likely see import bans by many countries.
Of course, attitudes can change.
Particularly if the ravages of avian flu raise the price of poultry to exorbitant levels. We live in an increasingly food-insecure world, and the future spread of diseases like avian influenza, African Swine Fever, and a host of others could seriously endanger the food supply.
And, as we've seen with poorly matched vaccines, that could open the door to potential viral escape. But the editing of two additional genes (ANP32B and ANP32E) appears to mitigate that risk. At least in chicken cell cultures.For now, the results from CRISPR editing of a single poultry gene (ANP32A) are encouraging, but not a home run. Chickens show increased resistance to influenza infection, but not full immunity.
Due to its length, and technical nature, I've just reproduced the link and abstract to the paper. Follow the link to read it in its entirety.
For a less-technical summary, I've included the press release from The University of Edinburgh. I'll have a postscript after the break.
Creating resistance to avian influenza infection through genome editing of the ANP32 gene familyAlewo Idoko-Akoh, Daniel H. Goldhill, Carol M. Sheppard, Dagmara Bialy, Jessica L. Quantrill, Ksenia Sukhova, Jonathan C. Brown, Samuel Richardson, Ciara Campbell, Lorna Taylor, Adrian Sherman, Salik Nazki, Jason S. Long, Michael A. Skinner, Holly Shelton, Helen M. Sang, Wendy S. Barclay & Mike J. McGrew
Nature Communications volume 14, Article number: 6136 (2023) Cite this article
Abstract
Chickens genetically resistant to avian influenza could prevent future outbreaks. In chickens, influenza A virus (IAV) relies on host protein ANP32A. Here we use CRISPR/Cas9 to generate homozygous gene edited (GE) chickens containing two ANP32A amino acid substitutions that prevent viral polymerase interaction. After IAV challenge, 9/10 edited chickens remain uninfected. Challenge with a higher dose, however, led to breakthrough infections.Breakthrough IAV virus contained IAV polymerase gene mutations that conferred adaptation to the edited chicken ANP32A. Unexpectedly, this virus also replicated in chicken embryos edited to remove the entire ANP32A gene and instead co-opted alternative ANP32 protein family members, chicken ANP32B and ANP32E. Additional genome editing for removal of ANP32B and ANP32E eliminated all viral growth in chicken cells. Our data illustrate a first proof of concept step to generate IAV-resistant chickens and show that multiple genetic modifications will be required to curtail viral escape.
Gene-edited chickens in fight against bird flu
Scientists have used gene editing techniques to identify and change parts of chicken DNA that could limit the spread of the bird flu virus in the animals.Researchers were able to restrict – but not completely block – the virus from infecting chickens by altering a small section of their DNA.
The birds showed no signs that the change in their DNA had any impact on their health or wellbeing.
The findings are an encouraging step forward, but experts highlight that further gene edits would be needed to produce a chicken population which cannot be infected by bird flu – one of the world's most costly animal diseases.
Gene editing
Scientists from University of Edinburgh, Imperial College London and the Pirbright Institute bred the chickens using gene editing techniques to alter the section of DNA responsible for producing the protein ANP32A. During an infection, flu viruses hijack this molecule to help replicate themselves.
When the ANP32A gene-edited chickens were exposed to a normal dose of the H9N2-UDL strain of avian influenza virus – commonly known as bird flu – 9 out of 10 birds remained uninfected and there was no spread to other chickens.
Partial protectionThe research team then exposed the gene-edited birds to an artificially high dose of avian influenza virus to further test their resilience.
When exposed to the high dose, half of the group – 5 out of 10 birds – became infected. However, the gene edit did provide some protection, with the amount of virus in the infected gene-edited chickens much lower than the level typically seen during infection in non-gene-edited chickens.
The gene edit also helped to limit onward spread of the virus to just one of four non-gene-edited chickens placed in the same incubator. There was no transmission to gene-edited birds.
Viral evolution
Scientists found that in the ANP32A gene-edited birds, the virus had adapted to enlist the support of two related proteins – ANP32B and ANP32E – to replicate.
Following lab tests, scientists found that some of the mutations enabled the virus to utilise the human version of ANP32, but its replication remained low in cell cultures from the human airway.
Experts say that additional genetic changes would be needed for the virus to infect and spread effectively in humans.
However, the findings demonstrate that the single ANP32A gene edit is not robust enough for application in the production of chickens, according to the team.
Further editsTo prevent the emergence of escape viruses – viruses that adapt to evade the gene edit and cause infection – the research team next targeted additional sections of DNA responsible for producing all three proteins – ANP32A, ANP32B and ANP32E – inside lab-grown chicken cells.
In cell cultures in the lab, growth of the virus was successfully blocked in cells with the three gene edits.
The next step will be to try to develop chickens with edits to all three genes. No birds have been produced yet.
The study highlights the importance of responsible gene editing and the need to be alert to the risks of driving viral evolution in unwanted directions if complete resistance is not achieved, experts say.
Bird flu is a major global threat, with a devastating impact in both farmed and wild bird populations. In the UK alone, the current outbreak of H5N1 bird flu has decimated seabird populations and cost the poultry industry more than £100 million in losses.
In rare instances, mutations in the bird flu virus allow it to infect people and cause serious illness. Efforts to control the spread of the disease are urgently needed.
Bird flu is a great threat to bird populations. Vaccination against the virus poses a number of challenges, with significant practical and cost issues associated with vaccine deployment. Gene-editing offers a promising route towards permanent disease resistance, which could be passed down through generations, protecting poultry and reducing the risks to humans and wild birds. Our work shows that stopping the spread of avian influenza in chickens will need several simultaneous genetic changes. - Professor Mike McGrewThe study’s principal investigator, from the University of Edinburgh’s Roslin InstituteThis work is an exciting collaboration that fuses our expertise in virology with the world-leading genetic capability at the Roslin Institute. Although we haven’t yet got the perfect combination of gene edits to take this approach into the field, the results have told us a lot about how influenza virus functions inside the infected cell and how to slow its replication. - Professor Wendy Barclay Imperial College London
The research was funded by UKRI-BBSRC, which also provides strategic funding to The Roslin Institute, and was supported by Edinburgh Innovations, the University’s commercialisation service.
