Used in COVID shots, mRNA may help rid the body of HIV

The technology that powered COVID vaccines may also lead scientists to a cure for HIV. Using mRNA, Australian researchers said they were able to trick the virus to come out of hiding, a crucial step in ridding the body of it entirely.
The research, published last week in Nature Communications, is still preliminary and so far has been shown to be successful only in a lab. But it suggests that mRNA has potential far beyond its use in vaccines as a means to deliver therapies against stubborn adversaries.
Short for messenger RNA, mRNA is a set of instructions for a gene. In the case of COVID vaccines, the instructions were for a piece of the coronavirus. In the new study, they are for molecules key to targeting HIV.
Dr. Sharon Lewin, director of the Doherty Institute at the University of Melbourne, who led the study, called mRNA a 'miraculous' tool 'to deliver things that you want into places that were not possible before.'
Vaccines deploying mRNA instruct the body to produce a fragment of the virus, which then sets off the body's immune response. In the United States, the shots were initially hailed for turning back the pandemic, then viewed by some with suspicion and fear. Some officials, including Health Secretary Robert F. Kennedy Jr., have falsely said that they are highly dangerous and even deadly.
Last week, the Department of Health and Human Services sought to limit the vaccine's availability to pregnant women, children and healthy younger adults. The administration also canceled a nearly $600 million contract with the drugmaker Moderna to develop an mRNA shot for humans against bird flu.
'The fear right now is not rational,' Lewin said, adding that 'mRNA vaccines have been given to millions of people around the world, so we have a very good understanding of their risks.'
The new study describes the use of mRNA as a tool to flush HIV out of its hiding places. Other uses could involve providing proteins missing from those with certain diseases or correcting genetic errors.
Frauke Muecksch, a virologist at Heidelberg University in Germany who was not involved in the work, called mRNA a 'promising, absolutely powerful technology.'
Although most people may have only heard of mRNA's use in science during the pandemic, scientists have been working with it for more than 20 years, she said.
'I think it's not just therapeutically very powerful, but also for basic science, for research, it opens up a lot of avenues,' she added.
Potent antiretroviral drugs can now control HIV, suppressing it to undetectable levels. Still, minute amounts of the virus lie dormant in so-called reservoirs, waiting for an opportunity to resurge. A cure for HIV would involve ferreting out all of this virus and destroying it, a strategy that has been called 'shock and kill.'
A significant hurdle is that the virus lies dormant in a particular type of immune cell, called a resting CD4 cell. Because these cells are inactive, they tend to be unresponsive to drugs.
The few drugs scientists have previously used to rouse the virus in these cells were not specific to HIV and had unwanted side effects.
'It's fair to say the field's been a little bit stuck,' said Brad Jones, a viral immunologist at Weill Cornell Medicine who was not involved in the latest research.
In 2022, Jones and his colleagues found that the immune boost from the mRNA vaccines awakened latent HIV in people living with the virus. (Other research has shown that mRNA vaccines also activated dormant viruses including Epstein Barr.)
'You get just a little bit of a gentle nudge with some of these vaccines, and it's enough to coax some of these latent viruses out so they can be killed,' Jones said.
Lewin and her colleagues had for years experimented with other ways to activate HIV but had no luck in resting cells. Seeing the success of the COVID vaccines, which used lipid nanoparticles — tiny spheres of fat — containing mRNA, her team tested similar particles.
They used the particles to deliver two different sets of molecules: Tat, which is adept at switching HIV on, and CRISPR, a tool that can 'edit' genes.
The researchers showed that in resting immune cells from people living with HIV, the approach coaxed the virus out of dormancy.
'It's very, very hard to deal with these cells, so I think this really targeting the right population of cells is what makes this paper special,' Muecksch said.
It's unclear whether the new approach can successfully awaken all of the dormant HIV in the body, and what side effects it might produce.
Lewin said that 'mRNA will almost certainly have some adverse effects, as every drug does, but we will investigate that systematically, as we do for any new drug.' In this case, she said, side effects may be more acceptable to people living with HIV than having to take medications for the rest of their lives.
The researchers plan to test the method in HIV-infected animals next, before moving into clinical trials.
This article originally appeared in The New York Times.

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Mass. considers scrapping religious exemptions for vaccinations

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Gizmodo

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When Will Genetically Modifying Our Children Go Mainstream?

In late May, several scientific organizations, including the International Society for Cell and Gene Therapy (ISCT), banded together to call for a 10-year moratorium on using CRISPR and related technologies to pursue human heritable germline editing. The declaration also outlined practical steps that countries and research institutions could take to discourage this sort of experimentation, such as strengthening regulations tied to gene editing. 'Germline editing has very serious safety concerns that could have irreversible consequences,' said Bruce Levine, a cancer gene therapy researcher at the University of Pennsylvania and former president of the ISCT, in a statement. 'We simply lack the tools to make it safe now and for at least the next 10 years.' Newer technologies such as CRISPR have made gene editing easier, cheaper, and more practical to carry out in a variety of species, humans included. That reality has made heritable germline editing—altering egg, sperm, and embryos such that they can be passed down to offspring—more feasible than ever. In November 2018, Chinese scientist He Jiankui thrust this issue into the limelight when he announced that his team modified the genes of several human embryos using CRISPR, then implanted them successfully in women volunteers. Eventually three children were born with the modifications, intended to confer natural immunity to HIV infection. He deliberately flouted ethical guidelines and the law in his research, such as doctoring lab results so that HIV-positive men could father the children (according to He, the children were born without HIV and appeared to have avoided any related health issues). He's experiments were roundly condemned by the scientific community and he ultimately served a three-year prison term for his actions, which ended in 2022. Upon release, He went back to working in the gene-editing field, though he promised to abide by domestic and international rules. The episode showed that human heritable germline editing is already clearly possible today, but not necessarily ethical to carry out. Indeed, many scientists and bioethicists believe we're not ready to go down that path just yet. For this Giz Asks, we reached out to several bioethicists to get their take on the moratorium, and more broadly, on the question of when we should be able to genetically modify children, if ever. Founding head of the Division of Medical Ethics at New York University's Grossman School of Medicine's Department of Population Health. I've been thinking about that question for well over 40 years. We didn't always have the technology to go in and modify genes in an egg, sperm, embryo, or fetus for that matter. But it's certainly the case that people have been thinking hard about trying to genetically alter and improve children, probably back to the Greeks. We know that in modern times, Nazi Germany was home to race hygiene theory and a form of eugenics; they would have been very interested in creating better babies. They did have the Lebensborn Program where they tried to force women and men that they deemed especially genetically fit to breed and have kids. It's not really clear whatever happened to those kids. But it's a form, if you will, of trying to get the right genes into your offspring and get them passed along into the future. They practiced that. And we had versions of that in the U.S., believe it or not. We actually had awards given at state fairs to families that were seen as eugenically the best and trying to encourage those families to have bigger families. That's an idea that's still rattling around today, by the way, in the mouths of Donald Trump, Elon Musk, Stephen Miller, etc. Many in the current Trump administration are very concerned about minorities becoming the majority in the U.S. In any event, these are old fashioned ideas, often fueled by dreams of eugenics, shifting the population in the future toward healthier, more competent, more physically able people, trying to get people of the right race or ethnicity so that the society's makeup is proper. They don't rely on engineering a gene. There's no CRISPR. There's nobody going in there and trying to penetrate the cell wall to insert genetic information. But those are just new ways to think about ideas that have been around for a long time. So if you ask me, will we see genetic engineering of children aimed at their improvement? I say yes, undoubtedly. Now when? I'm not sure what the answer to that is. Right now, we have some crude tools. We are seeing some efforts to use gene therapy in kids to repair diseases of their bodies, not things that would be inherited. They work a bit, but I wouldn't say we're really at the sort of utopia of being able to reliably get rid of in a person or a child, sickle cell or other major diseases. The tools, despite a lot of hype and a lot of maybe press release journalism, are not quite there yet to really say we can even do a good job repairing disease in an existing kid. So when it comes to trying to use tools to modify an embryo, I'm going to say flat out we're at least 10 years away from that in any serious way that could be considered safe, targeted, and likely to produce the outcome you want. So the big restriction now is safety. I think we'll get past safety, but it is a reason right now not to do anything. Now, what else might become an objection if we did have accurate, sophisticated tools? I think the first is access. If you make better kids, but only some people can afford it, that wouldn't be fair. And that in itself would be unjust. And you might wind up creating two classes or more of humans on Earth, the genetically engineered superior people and others. And this obviously is a theme all over science fiction. Old-timers will remember the Wrath of Khan from Star Trek for their take on what happens when you get a super genetically engineered race. There's Gattaca, another movie that explored this. But I'm going to say this somewhat controversially. Fairness in access never stopped a technology from going forward. When the rich and the middle class want it, they're not stopped by the fact that the poor can't get it. I would like to see provisions made to say we shouldn't move forward unless those technologies are available to those who want them regardless of cost. But I don't think that's going to happen. It's just never happened. So access is an issue, but I don't think it's a game-breaker for improving your kids. People also say, well, how will we improve? I mean, what's the best state? We can't agree on that. So will we really improve kids? There may be things we disagree about as to whether they're really improvements. Would it be an improvement to diminish pigment in black people? Try and make them less dark. We can certainly see that argued. There are plenty in the deaf community who say, well, deafness is not really something you have to get rid of or try to improve by genetically engineering hearing to make it better. They can get around the world deaf using a different language and different institutions. But there are clearly things that it would be nice to genetically improve in kids. Immunity would be great. We do it now with vaccines. It would be great to find the right genes, tweak them, and build stronger immune systems. It would be great to make sure that we try our best to diminish the extreme pain, that some of us suffer not just as disease, but with respect to certain stimuli. I'm not saying we should genetically eliminate all pain. That would probably put us in danger, but we don't quite have to suffer the way we do. My point being, the fact that we don't agree on everything as to what would be an improvement doesn't mean that we can't agree on anything. The last thing I'll say is this. When you try to make better kids, I think one last concern is: Are you going to make the children have less options rather than more? So if I considered it an improvement in a child to make them a giant, or to make them a tennis player, or to try and figure out perhaps some weird appearance that would make them a celebrity, I'm condemning the child to my choice. They don't have the freedom to run their own life. They don't have the ability to choose what they want to do. I tighten down their future by narrowing the kinds of traits they have. That, I think, is a legitimate objection. We have to think hard about that. Many of the things we do environmentally, learn to read better, learn to do exercise, learn to play games, these are skills that expand capacities in our children, and may in fact be values that are then passed on to future generations. But they don't wind up creating kids who are less capable because of those interventions. That's where genetic change has to be watched very closely. So the bottom line of this gigantic speech is yes, we will see genetic modification of our children. It will come. There are traits that people will eagerly try to put into their kids in the future. They will try to design out genetic diseases, get rid of them. They will try to build in capacities and abilities that they agree are really wonderful. Will we hang up these interventions on ethical grounds? For the most part, no, would be my prediction, But not within the next 10 years. The tools are still too crude. Associate professor of bioethics at Case Western Reserve University's School of Medicine There are children with genetic modifications walking around today, children like KJ, who was treated with personalized CRISPR gene editing at just six months old. There are now kids who are free of sickle cell disease symptoms through CRISPR therapy, the first one ever approved by the FDA. All of these children are 'genetically modified,' and they and their parents couldn't be happier about it. What other conditions could and should be treated through genetic modifications? That's a question that scientists are actively working on, and that social scientists like me are talking about with patients, parents, and communities—because we and they think it's really important for them to be part of those decisions. These 'somatic' gene editing treatments that are already being used aren't the kind that is passed down through our reproductive cells, the germline. Heritable gene modification would involve embryos, eggs, or sperm, or even possibly other cells that could be turned into these kinds of cells. A technology currently being researched, called in vitro gametogenesis, could use gene editing to turn skin cells into reproductive cells, allowing families with infertility to have their own genetically related children. And of course, there are scientists looking at the possibility of editing reproductive cells to allow couples who carry the genes for severe diseases to conceive children without those conditions. Many ethicists and scientists have drawn a hard line between heritable and non-heritable gene editing, but in practice it's not nearly so clear-cut. Off-target effects of gene editing are difficult to predict or control, so there is a chance that reproductive cells could be changed by treatments aimed at other organ systems. Fetal gene editing, which could help babies with some conditions be born with few or no symptoms, will also involve the pregnant bodies of their mothers; those adults could host edited cells even after the pregnancy ends, possibly affecting their future children too. Families dealing with genetic conditions that cause great suffering for their children don't necessarily see a problem with eliminating those conditions forever with heritable gene editing. On the other hand, some people living with genetic conditions, such as deafness or autism, see no reason for treating their condition with gene editing, heritable or not, because their biggest problems come not from the condition itself but from the way society treats them. So there are many questions to be asked about all forms of genetic modification, and how they will be developed and implemented. All the gene editing treatments that exist now or are being imagined over the next decade, heritable or not, involve exorbitant cost and will be inaccessible to most people worldwide. It will be crucial to balance the excitement of these novel technologies with attention to questions of justice, developing new treatments with an eye toward both accessibility and the priorities of those most affected. The only way to do this is to bring more voices into conversation with one another: people living with genetic conditions, scientists and doctors, policymakers of all kinds, and members of the public. Although gene editing is an amazing tool to add to our kit, the work of building more robust healthcare and support for families carrying or living with genetic conditions doesn't begin or end with genetic modification. Bioethicist, sociologist, and executive director of the Institute for Ethics and Emerging Technologies. Yes we should, when it's safe, effective, and voluntary. Calls to permanently ban the creation of genetically modified children often rest on fear, not facts. They mirror past moral panics over interracial marriage, in vitro fertilization, and birth control—all technologies or choices once deemed unnatural or dangerous, and now widely accepted. We should be wary of arguments dressed up as ethics but rooted in anxiety about change. That doesn't mean anything goes. Like any powerful technology, gene editing must be tightly regulated for safety and efficacy. But the agencies we already trust to regulate medicine—the FDA, NIH, and institutional review boards—are largely capable of doing that. We don't need a bioethics priesthood or a new bureaucracy to police reproductive decisions. We need science-based oversight, individual consent, and protection from coercion. One of the loudest objections to genetic editing is the specter of 'eugenics.' But if eugenics means state control over reproduction, then the lesson of the 20th century is to defend reproductive freedom, not curtail it. Governments should not tell parents what kinds of kids to have. Preventing parents from using safe, approved gene therapies to reduce suffering or enhance their children's lives is a strange way to honor that lesson. They should give parents access to all the information and technology for the choices they make. True reproductive liberty includes the right to use the best science available to ensure a child's health. Another objection is that genetic modification could harm people who would rather not participate. But this 'perfection anxiety' ignores how all medical advances shift social norms. We didn't stop improving dental care because it made bad teeth less acceptable. And a healthier society has not led to less compassion for those who remain sick or disabled—if anything, it's strengthened the case for inclusion and support. The goal should be equitable access, not frozen norms. We do need to ensure that parents can access all the gene therapies that actually provide potential benefits for children. Governments with universal healthcare will need to make tough choices about what to cover and what not to cover. For instance, the National Health Service should make gene therapy to remove lethal, painful conditions available for all Britons, but parents may need to pay for medical tourism to some offshore clinic if they want to tweak their embryo's eye color. What about risks we can't foresee? Of course there will be some. All new medical therapies come with uncertainties. That's why we have trials, regulation, and post-market surveillance. There's no reason genetic therapies should be held to an impossibly higher standard. We should start with animal models, and proceed to the most morally defensible gene tweaks, lethal and painful conditions. Over time, as the safety of the techniques are better understood, we can expand the scope of therapeutic choices. Some worry that genetically modified children could disrupt our ideas of family or humanity. But those concepts have already been revolutionized—by urbanization, feminism, economic precarity, and social movements. The family of today would be unrecognizable to most people in 1800. If genetic technologies change our values again, it won't be the first time. Liberal democracies don't freeze culture in place—they ensure people have the freedom to shape it. Ultimately, the question isn't whether we should allow genetically modified children. It's whether we trust parents to make mostly good choices under the oversight of regulators and doctors. We should, because most parents have their children's best interests in mind, as they perceive them. That's why we allow parents to raise their own children in the first place. And we should ensure those choices are equitably available to all, not outlawed out of fear. If we ever find genetic tweaks to reduce suffering, enhance capability, or prevent devastating disease—and we can do so safely and ethically—the real moral failure would be to prohibit it. A Canadian bioethicist and environmentalist currently teaching at the University of Toronto. Well, there's a big difference between genetic enhancement and treatment. And with enhancement, I think we're nowhere near a point where we should be even considering that. But with treatment, the large ethical issue right now is something like single gene mutation. So something like Huntington's disease, muscular dystrophy, or similar diseases, could it be justified to edit the gene for that? The challenge is we don't fully understand all the things. We don't know what we don't know, to put it bluntly. And with germline editing, the changes we would be making are permanent and they run through many generations ahead. So, yes, being able to prevent deadly or debilitating illnesses is absolutely something wonderful. But having said that, you obviously don't have consent of the person who will be born, but you also don't have consent of the generations that come after that. And if there is complications or unexpected problems, you can have an inheritance that just keeps running through generations. But here's the thing with this moratorium; to what end? You can call for a moratorium, but if no one's focusing on anything, if there's no research, no planning, no social discourse, there's just a lot of people with different opinions, and everything gets shelved for 10 years. I'm not sure that's going to be particularly useful. It sounds great if it's going to be 10 concentrated years on building consensus and public engagement and those types of things, but I don't think that's what would actually happen. And also, I'm sure you've noticed, the world's not in good shape, and Western culture is not of one mind these days. And with the ruptures, particularly in the United States, there's a lot of division in Western culture of how people see things. And I'm just not convinced that a moratorium, that people would make use of it in a constructive way. It really needs a coordinated plan, and I'm not sure there is one. So I do see that as quite a problem. The other thing is, we're dealing with high-income countries. So when we look at potential for CRISPR-Cas9 and gene editing, we're dealing with a very small percentage of the world's population. I'm going to guess that it's maybe 15% to 20% of the world's population, because most of the population of the world has no access to things like this and never will. Not never will, but in the foreseeable future, they won't. And I think that's something we miss a lot of the time. And the biggest ethical problem in the world today is not gene editing. It's just access to healthcare. And this doesn't do anything in those domains whatsoever. So from a justice point of view, that is a concern. And I'm going to sound cynical here. Emerging medical technologies are not motivated largely by the social sector. They're motivated by marketing and market forces. So if people can make money on this, somehow, someway, people will proceed. And if gene editing is illegal in Canada and the U.S. and Western Europe and Australia, there's a lot of countries that don't fall into that. And you can set up shop anywhere. Equatorial Guinea or other places are not going to be worried about things like this. They've got enough problems on their hands. And there's a lot of countries out there where this would not be easily called. So I support the essence of it. And I can see why people want to do it. I'm just not convinced it's all that feasible. I think what makes more sense is just not having any germline editing until we have a larger consensus about this technology.

New York Times

9 hours ago

• New York Times

‘I Feel Like I've Been Lied To': When a Measles Outbreak Hits Home

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