New gene therapy to target airway and lungs via nasal spray
For gene therapy to work well, therapeutic molecules need to be efficiently delivered to the correct locations in the body. It is commonly done by using adeno-associated viruses (AAV) gene therapy.
To improve the AAV's ability to deliver therapeutics specifically to the lungs and airway, researchers at the Mass General Brigham engineered a new version, called AAV.CPP.16, which can be administered with a nasal spray.
In preclinical models, AAV.CPP.16 outperformed previous versions by more effectively targeting the airway and lungs and showing promise for respiratory and lung gene therapy, said the researchers in the paper published in the journal Cell Reports Medicine.
"We noticed that AAV.CPP.16, which we initially engineered to enter the central nervous system, also efficiently targeted lung cells," said senior author FengFeng Bei, from the Department of Neurosurgery at Brigham and Women's Hospital.
"This prompted us to further investigate AAV.CPP.16 for intranasal gene delivery to the respiratory airways," Bei added.
In the study, AAV.CPP.16 outperformed previous versions (AAV6 and AAV9) in cell culture, mouse models, and non-human primate models.
'Our findings highlight AAV.CPP.16 as a promising vector for respiratory and lung gene therapy,' the team said.
They then used the more efficient tool to deliver scar-preventing gene therapy for pulmonary fibrosis, using a mouse model of the respiratory disease.
They also used the tool to deliver gene therapy for a viral infection, where the therapy prevented the replication of the SARS-CoV-2 virus in a mouse model of Covid-19.
"Although further research is needed, our findings suggest that intranasal AAV.CPP.16 has strong translational potential as a promising delivery tool for targeting the airway and lung," said Bei.
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Time of India
6 hours ago
- Time of India
How conspiracy theories about COVID's origins are hampering our ability to prevent the next pandemic
Sydney : In late June, the Scientific Advisory Group for the Origins of Novel Pathogens (SAGO), a group of independent experts convened by the World Health Organization (WHO), published an assessment of the origins of COVID . The report concluded that although we don't know conclusively where the virus that caused the pandemic came from: "a zoonotic origin with spillover from animals to humans is currently considered the best supported hypothesis." SAGO did not find scientific evidence to support "a deliberate manipulation of the virus in a laboratory and subsequent biosafety breach". This follows a series of reports and research papers since the early days of the pandemic that have reached similar conclusions: COVID most likely emerged from an infected animal at the Huanan market in Wuhan , and was not the result of a lab leak. But conspiracy theories about COVID's origins persist. And this is hampering our ability to prevent the next pandemic. Attacks on our research As experts in the emergence of viruses, we published a peer-reviewed paper in Nature Medicine in 2020 on the origins of SARS-CoV-2, the virus that causes COVID. Like SAGO, we evaluated several hypotheses for how a novel coronavirus could have emerged in Wuhan in late 2019. We concluded the virus very likely emerged through a natural spillover from animals - a "zoonosis" - caused by the unregulated wildlife trade in China . Since then, our paper has become a focal point of conspiracy theories and political attacks. The idea SARS-CoV-2 might have originated in a laboratory is not, in itself, a conspiracy theory. Like many scientists, we considered that possibility seriously. And we still do, although evidence hasn't emerged to support it. But the public discourse around the origin of the pandemic has increasingly been shaped by political agendas and conspiratorial narratives. Some of this has targeted our work and vilified experts who have studied this question in a data-driven manner. A common conspiracy theory claims senior officials pressured us to promote the "preferred" hypothesis of a natural origin, while silencing the possibility of a lab leak. Some conspiracy theories even propose we were rewarded with grant funding in exchange. These narratives are false. They ignore, dismiss or misrepresent the extensive body of evidence on the origin of the pandemic. Instead, they rely on selective quoting from private discussions and a distorted portrayal of the scientific process and the motivations of scientists. So what does the evidence tell us? In the five years since our Nature Medicine paper, a substantial body of new evidence has emerged that has deepened our understanding of how SARS-CoV-2 most likely emerged through a natural spillover. In early 2020, the case for a zoonotic origin was already compelling. Much-discussed features of the virus are found in related coronaviruses and carry signatures of natural evolution. The genome of SARS-CoV-2 showed no signs of laboratory manipulation. The multi-billion-dollar wildlife trade and fur farming industry in China regularly moves high-risk animals, frequently infected with viruses, into dense urban centres. It's believed that SARS-CoV-1, the virus responsible for the SARS outbreak, emerged this way in 2002 in China's Guangdong province. Similarly, detailed analyses of epidemiological data show the earliest known COVID cases clustered around the Huanan live-animal market in Wuhan, in the Hubei province, in December 2019. Multiple independent data sources, including early hospitalisations, excess pneumonia deaths, antibody studies and infections among health-care workers indicate COVID first spread in the district where the market is located. In a 2022 study we and other experts showed that environmental samples positive for SARS-CoV-2 clustered in the section of the market where wildlife was sold. In a 2024 follow-up study we demonstrated those same samples contained genetic material from susceptible animals - including raccoon dogs and civets - on cages, carts, and other surfaces used to hold and transport them. This doesn't prove infected animals were the source. But it's precisely what we would expect if the market was where the virus first spilled over. And it's contrary to what would be expected from a lab leak. These and all other independent lines of evidence point to the Huanan market as the early epicentre of the COVID pandemic. Hindering preparedness for the next pandemic Speculation and conspiracy theories around the origin of COVID have undermined trust in science. The false balance between lab leak and zoonotic origin theories assigned by some commentators has added fuel to the conspiracy fire. This anti-science agenda, stemming in part from COVID origin conspiracy theories, is being used to help justify deep cuts to funding for biomedical research, public health and global aid. These areas are essential for pandemic preparedness. In the United States this has meant major cuts to the US Centers for Disease Control and the National Institutes of Health , the closure of the US Agency for International Development , and withdrawal from the WHO. Undermining trust in science and public health institutions also hinders the development and uptake of life-saving vaccines and other medical interventions. This leaves us more vulnerable to future pandemics. The amplification of conspiracy theories about the origin of COVID has promoted a dangerously flawed understanding of pandemic risk. The idea that a researcher discovered or engineered a pandemic virus, accidentally infected themselves, and unknowingly sparked a global outbreak (in exactly the type of setting where natural spillovers are known to occur) defies logic. It also detracts from the significant risk posed by the wildlife trade. In contrast, the evidence-based conclusion that the COVID pandemic most likely began with a virus jumping from animals to humans highlights the very real risk we increasingly face. This is how pandemics start, and it will happen again. But we're dismantling our ability to stop it or prepare for it. (The Conversation)
NDTV
6 hours ago
- NDTV
How Covid Origin Theories Are Hampering Our Ability To Prevent Next Pandemic
Sydney: In late June, the Scientific Advisory Group for the Origins of Novel Pathogens (SAGO), a group of independent experts convened by the World Health Organization (WHO), published an assessment of the origins of COVID. The report concluded that although we don't know conclusively where the virus that caused the pandemic came from: a zoonotic origin with spillover from animals to humans is currently considered the best supported hypothesis. SAGO did not find scientific evidence to support "a deliberate manipulation of the virus in a laboratory and subsequent biosafety breach". This follows a series of reports and research papers since the early days of the pandemic that have reached similar conclusions: COVID most likely emerged from an infected animal at the Huanan market in Wuhan, and was not the result of a lab leak. But conspiracy theories about COVID's origins persist. And this is hampering our ability to prevent the next pandemic. Attacks on our research As experts in the emergence of viruses, we published a peer-reviewed paper in Nature Medicine in 2020 on the origins of SARS-CoV-2, the virus that causes COVID. Like SAGO, we evaluated several hypotheses for how a novel coronavirus could have emerged in Wuhan in late 2019. We concluded the virus very likely emerged through a natural spillover from animals - a "zoonosis" - caused by the unregulated wildlife trade in China. Since then, our paper has become a focal point of conspiracy theories and political attacks. The idea SARS-CoV-2 might have originated in a laboratory is not, in itself, a conspiracy theory. Like many scientists, we considered that possibility seriously. And we still do, although evidence hasn't emerged to support it. But the public discourse around the origin of the pandemic has increasingly been shaped by political agendas and conspiratorial narratives. Some of this has targeted our work and vilified experts who have studied this question in a data-driven manner. A common conspiracy theory claims senior officials pressured us to promote the " preferred" hypothesis of a natural origin, while silencing the possibility of a lab leak. Some conspiracy theories even propose we were rewarded with grant funding in exchange. These narratives are false. They ignore, dismiss or misrepresent the extensive body of evidence on the origin of the pandemic. Instead, they rely on selective quoting from private discussions and a distorted portrayal of the scientific process and the motivations of scientists. So what does the evidence tell us? In the five years since our Nature Medicine paper, a substantial body of new evidence has emerged that has deepened our understanding of how SARS-CoV-2 most likely emerged through a natural spillover. In early 2020, the case for a zoonotic origin was already compelling. Much-discussed features of the virus are found in related coronaviruses and carry signatures of natural evolution. The genome of SARS-CoV-2 showed no signs of laboratory manipulation. The multi-billion-dollar wildlife trade and fur farming industry in China regularly moves high-risk animals, frequently infected with viruses, into dense urban centres. It's believed that SARS-CoV-1, the virus responsible for the SARS outbreak, emerged this way in 2002 in China's Guangdong province. Similarly, detailed analyses of epidemiological data show the earliest known COVID cases clustered around the Huanan live-animal market in Wuhan, in the Hubei province, in December 2019. Multiple independent data sources, including early hospitalisations, excess pneumonia deaths, antibody studies and infections among health-care workers indicate COVID first spread in the district where the market is located. In a 2022 study we and other experts showed that environmental samples positive for SARS-CoV-2 clustered in the section of the market where wildlife was sold. In a 2024 follow-up study we demonstrated those same samples contained genetic material from susceptible animals - including raccoon dogs and civets - on cages, carts, and other surfaces used to hold and transport them. This doesn't prove infected animals were the source. But it's precisely what we would expect if the market was where the virus first spilled over. And it's contrary to what would be expected from a lab leak. These and all other independent lines of evidence point to the Huanan market as the early epicentre of the COVID pandemic. Hindering preparedness for the next pandemic Speculation and conspiracy theories around the origin of COVID have undermined trust in science. The false balance between lab leak and zoonotic origin theories assigned by some commentators has added fuel to the conspiracy fire. This anti-science agenda, stemming in part from COVID origin conspiracy theories, is being used to help justify deep cuts to funding for biomedical research, public health and global aid. These areas are essential for pandemic preparedness. In the United States this has meant major cuts to the US Centers for Disease Control and the National Institutes of Health, the closure of the US Agency for International Development, and withdrawal from the WHO. Undermining trust in science and public health institutions also hinders the development and uptake of life-saving vaccines and other medical interventions. This leaves us more vulnerable to future pandemics. The amplification of conspiracy theories about the origin of COVID has promoted a dangerously flawed understanding of pandemic risk. The idea that a researcher discovered or engineered a pandemic virus, accidentally infected themselves, and unknowingly sparked a global outbreak (in exactly the type of setting where natural spillovers are known to occur) defies logic. It also detracts from the significant risk posed by the wildlife trade. In contrast, the evidence-based conclusion that the COVID pandemic most likely began with a virus jumping from animals to humans highlights the very real risk we increasingly face. This is how pandemics start, and it will happen again. But we're dismantling our ability to stop it or prepare for it. (Author: , NHMRC Leadership Fellow and Professor of Virology, University of Sydney; Andrew Rambaut, Professor of Molecular Evolution, University of Edinburgh; Kristian Andersen, Professor; Director of Infectious Disease Genomics, The Scripps Research Institute, and Robert Garry, Professor, Department of Microbiology and Immunology, Tulane University) (Disclaimer Statement: Edward C Holmes receives funding from the Australian Research Council and the National Health and Medical Research Council (Australia). He has received consultancy fees from Pfizer Australia and Moderna, and has previously held honorary appointments (for which he has received no renumeration and performed no duties) at the China CDC in Beijing and the Shanghai Public Health Clinical Center (Fudan University). Andrew Rambaut receives funding from The Wellcome Trust and the Gates Foundation. Kristian G. Andersen receives funding from the National Institutes of Health, the Centers for Disease Control and Prevention, and the Gates Foundation. He is on the Scientific Advisory Board of Invivyd, Inc. and has consulted on topics related to the COVID-19 pandemic and other infectious diseases. The views and opinions expressed in this publication are solely those of the author in their personal capacity and do not necessarily reflect the views, positions, or policies of Scripps Research, its leadership, faculty, staff, or its scientific collaborators or affiliates. Scripps Research does not endorse or take responsibility for any statements made in this piece. Robert Garry has received funding from the National Institutes of Health, the Coalition for Epidemic Preparedness Innovation, the Wellcome Trust Foundation, Gilead Sciences, and the European and Developing Countries Clinical Trials Partnership Programme. He is a co-founder of Zalgen Labs, a biotechnology company developing countermeasures for emerging viruses.) This article is republished from The Conversation under a Creative Commons license. Read the original article.
Hans India
12 hours ago
- Hans India
Drug for coeliac disease may help treat severe post-Covid syndrome in children
A drug designed to treat coeliac disease -- an autoimmune disorder primarily affecting the small intestine -- has shown promise for children affected with severe post-Covid syndrome, according to a small study. Covid infection, although rare in kids, leads to multisystem inflammatory syndrome in children (MIS-C) -- a serious condition that presents as high fevers, gastrointestinal symptoms, and life-threatening cardiac injury. The trial results, published in the journal Science Translational Medicine, showed that larazotide supported children in returning to normal activities more rapidly following Covid. "While our study is small, its results are powerful and have implications not only for MIS-C, but potentially for long Covid," said lead author Lael Yonker, co-director of the Cystic Fibrosis Center, at Mass General Brigham. "Our findings suggest that larazotide is safe and quickly resolves symptoms in children with MIS-C. We are now running a clinical trial to test whether larazotide may also be a useful therapy to treat patients with long Covid," Yonker added. Current MIS-C treatments are limited. Some patients receive general anti-inflammatory drugs, but many experience a rebound of symptoms after completing a course. Such drugs are not designed to target the sticky SARS-CoV-2 viral particles that may persist in the gut. On the other hand is the orally administered Larazotide, which targets the gut and strengthens intestinal barriers to limit the number of materials -- like SARS-CoV-2 viral particles -- that exit the intestines and enter circulation. To test larazotide's efficacy and safety as an MIS-C treatment, researchers conducted a double-blind clinical trial with 12 children experiencing early-stage MIS-C. Each patient randomly received either a placebo or larazotide four times daily for 21 days, then was tracked over six months of recovery. Children who received larazotide showed faster resolution of gastrointestinal symptoms, faster clearance of SARS-CoV-2 viral particles, and more rapid return to normal activities, the team said.
