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Drugs of the future will be easier and faster to make, thanks to mRNA − after researchers work out a few remaining kinks

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Drugs of the future will be easier and faster to make, thanks to mRNA – after researchers work out a few remaining kinks

Two hurdles mRNA drugs face are a short half-life and impurities that trigger immune responses.
BlackJack3D/iStock via Getty Images Plus

Li Li, UMass Chan Medical School

Vaccines have been reliably and affordably protecting people from diseases worldwide for centuries. Until the COVID-19 pandemic, however, vaccine development was still a long and idiosyncratic process. Traditionally, researchers had to tailor manufacturing processes and facilities for each vaccine candidate, and the scientific knowledge gained from one vaccine was often not directly transferable to another.

But the COVID-19 mRNA vaccines brought a new approach to vaccine development that has far-reaching implications for how researchers make drugs to treat many other diseases.

I am a biochemist, and my lab at UMass Chan Medical School focuses on developing better ways to use mRNA as a drug. Although there are many possibilities for what researchers can use mRNA to treat, some important limitations remain. Better understanding how mRNA-based drugs interact with the immune system and how they are degraded in human cells can help lead to safe, durable and effective treatments for a wide range of diseases.

Some basics of mRNA drugs

Messenger RNA, or mRNA, is made of four building blocks denoted by the letters A, C, G and U. The sequence of letters in an mRNA molecule conveys genetic information that directs how a protein is made.

An mRNA drug comprises two essential components: mRNA molecules, which code for desired proteins, and the lipid molecules – such as phospholipids and cholesterol – that encapsulate them. These mRNA-lipid nanoparticles, or LNPs, are tiny spheres about 100 nanometers in diameter that protect mRNA from degradation and facilitate its delivery into target cells.

Once inside cells, mRNA molecules instruct the cell’s machinery to produce the target protein required for a desired therapeutic effect. For example, the mRNA in the Pfizer-BioNTech and Moderna COVID-19 vaccines directs cells to produce a harmless version of the virus’ spike protein that trains the immune system to recognize and better prepare for potential infection.

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The science behind COVID-19 mRNA vaccines has been decades in the making.

From a drug development perspective, mRNA drugs offer significant advantages over traditional drugs because they are easily programmable. Hundreds of pounds of mRNA can be made from readily available DNA templates, such that producing a different mRNA drug is as simple as changing the corresponding DNA templates.

More importantly, different mRNA drugs produced by the same set of methods will have similar properties. They will be delivered to the same tissues, trigger similar levels of immune responses and degrade in similar ways. This predictability significantly reduces the development risks and financial costs of developing mRNA drugs.

In addition to being easy to program, mRNA drugs have several other unique properties. For example, just like the mRNAs your body naturally produces, therapeutic mRNAs have a short half-life in cells: about one day. As a result, current mRNA technology is ideal for treatments that aren’t meant to last long in the body.

This is why vaccines are popular candidates for mRNA technology: They provide long-term protection against disease after brief exposure to the drug with few side effects. There are currently more than 30 mRNA vaccine candidates, not including vaccines for COVID-19, in clinical trials.

Self vs. nonself

Another critical feature of mRNA drugs is their intrinsic ability to stimulate the immune system. This may sound paradoxical – after all, your cells already contain large amounts of mRNAs. Why would other mRNAs activate your immune system? How does your immune system distinguish between self and nonself mRNAs?

The first reason involves location. Therapeutic mRNAs enter cells using endosomes – sacs made of the cell’s membrane that take in materials from the cell’s environment. Your immune system can detect mRNA in endosomes because this is usually a sign of an RNA virus infection – cellular mRNAs normally don’t enter endosomes. When your immune system labels therapeutic mRNAs as viral material, it triggers a strong inflammatory response that can lead to severe side effects.

Diagram showing molecules entering a depression in the cell membrane which closes off to form a sac
Endocytosis is the process by which material outside the cell, such as mRNA molecules, is engulfed within the cell.
alfa md/iStock via Getty Images Plus

One solution to this problem is to modify mRNA’s building blocks – specifically, changing the U, or uridine, to its chemical cousins, pseudouridine and N1-methylpseudouridine. This subtle chemical change prevents the unwanted immune response while allowing the therapeutic mRNA to direct the cell to make the protein it encodes. The 2023 Nobel Prize in physiology or medicine was awarded to the scientists who made this breakthrough discovery. Both the Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines use this technique.

The second source of unwanted immune response is impurities from mRNA production. To prepare mRNA from a DNA template, scientists use a protein called RNA polymerase that tends to make a small amount of side product called double-stranded RNA. Unlike mRNA, which is single-stranded, double-stranded RNA has two chains that form a double helix. RNA viruses also form double-stranded RNA when they replicate, and exposing cells to double-stranded RNA can lead to a strong immune response.

Removing double-stranded RNA is challenging, especially at the industrial scale. Fortuitously, for mRNA vaccines, the residual amount of double-stranded RNA can stimulate the immune system to enhance antibody responses. However, for applications other than vaccines, a cleaner RNA product is necessary to reduce side effects.

Moving beyond vaccines

Although mRNA has the potential to transform drug development for various medical purposes, careful consideration is required to identify targets that align with the technology’s strengths.

For example, because there is currently a limit to how long mRNA can last in the body, treatments that need a protein to be present for only a short period of time to achieve a lasting therapeutic effect are ideal. One promising example in development is using mRNA that encodes CRISPR-Cas9 gene-editing proteins to knock out genes that cause specific diseases.

Researchers are exploring this strategy to develop a single-dose treatment for hereditary transthyretin amyloidosis, a rare genetic disease caused by the accumulation of misfolded proteins in the heart and nerves. This disease is an ideal target for mRNA-based CRISPR gene therapy because the target protein is produced by the liver. Because most drugs pass through the liver, this makes it easier to deliver CRISPR-Cas9 mRNA to its target. In the next few years, a new generation of more precise mRNA-based genome editing therapies will enter clinical trials.

Microscopy image of SARS-CoV-2 virus particles lining the a few vesicles in a cell
Because the virus that causes COVID-19 (gold) and other RNA viruses enter cells through endosomes, mRNA drug impurities can elicit similar immune responses.
NIAID/Flickr, CC BY

For treatments that need a specific protein to be present in the body for long periods of time or need to prompt little to no immune reaction, further advancements in mRNA technology are necessary to extend mRNA’s half-life and eliminate immune-triggering contaminants. Notable new developments in these areas include using computational algorithms to optimize mRNA sequences in ways that enhance their stability and engineering RNA polymerases that introduce fewer side products that may cause an immune response.

Further advancements have the potential to enable a new generation of safe, durable and effective mRNA therapeutics for applications beyond vaccines.The Conversation

Li Li, Assistant Professor of Biomedical Sciences, UMass Chan Medical School

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Measles can ravage the immune system and brain, causing long-term damage – a virologist explains

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theconversation.com – Peter Kasson, Professor of Chemistry and Biomedical Engineering, Georgia Institute of Technology – 2025-03-31 07:16:00

Measles infections send 1 in 5 people to the hospital.
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Peter Kasson, Georgia Institute of Technology

The measles outbreak that began in west Texas in late January 2025 continues to grow, with 400 confirmed cases in Texas and more than 50 in New Mexico and Oklahoma as of March 28.

Public health experts believe the numbers are much higher, however, and some worry about a bigger resurgence of the disease in the U.S. In the past two weeks, health officials have identified potential measles exposures in association with planes, trains and automobiles, including at Washington Dulles International Airport and on an Amtrak train from New York City to Washington, D.C. – as well as at health care facilities where the infected people sought medical attention.

Measles infections can be extremely serious. So far in 2025, 14% of the people who got measles had to be hospitalized. Last year, that number was 40%. Measles can damage the lungs and immune system, and also inflict permanent brain damage. Three in 1,000 people who get the disease die. But because measles vaccination programs in the U.S. over the past 60 years have been highly successful, few Americans under 50 have experienced measles directly, making it easy to think of the infection as a mere childhood rash with fever.

As a biologist who studies how viruses infect and kill cells and tissues, I believe it is important for people to understand how dangerous a measles infection can be.

Underappreciated acute effects

Measles is one of the most contagious diseases on the planet. One person who has it will infect nine out of 10 people nearby if those people are unvaccinated. A two-dose regimen of the vaccine, however, is 97% effective at preventing measles.

When the measles virus infects a person, it binds to specific proteins on the surface of cells. It then inserts its genome and replicates, destroying the cells in the process. This first happens in the upper respiratory tract and the lungs, where the virus can damage the person’s ability to breathe well. In both places, the virus also infects immune cells that carry it to the lymph nodes, and from there, throughout the body.

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Measles can wipe out immune cells’ ability to recognize pathogens.

What generally lands people with measles in the hospital is the disease’s effects on the lungs. As the virus destroys lung cells, patients can develop viral pneumonia, which is characterized by severe coughing and difficulty breathing. Measles pneumonia afflicts about 1 in 20 children who get measles and is the most common cause of death from measles in young children.

The virus can directly invade the nervous system and also damage it by causing inflammation. Measles can cause acute brain damage in two different ways: a direct infection of the brain that occurs in roughly 1 in 1,000 people, or inflammation of the brain two to 30 days after infection that occurs with the same frequency. Children who survive these events can have permanent brain damage and impairments such as blindness and hearing loss.

Yearslong consequences of infection

An especially alarming but still poorly understood effect of measles infection is that it can reduce the immune system’s ability to recognize pathogens it has previously encountered. Researchers had long suspected that children who get the measles vaccine also tend to have better immunity to other diseases, but they were not sure why. A study published in 2019 found that having a measles infection destroyed between 11% and 75% of their antibodies, leaving them vulnerable to many of the infections to which they previously had immunity. This effect, called immune amnesia, lasts until people are reinfected or revaccinated against each disease their immune system forgot.

Occasionally, the virus can lie undetected in the brain of a person who recovered from measles and reactivate typically seven to 10 years later. This condition, called subacute sclerosing panencephalitis, is a progressive dementia that is almost always fatal. It occurs in about 1 in 25,000 people who get measles but is about five times more common in babies infected with measles before age 1.

Researchers long thought that such infections were caused by a special strain of measles, but more recent research suggests that the measles virus can acquire mutations that enable it to infect the brain during the course of the original infection.

There is still much to learn about the measles virus. For example, researchers are exploring antibody therapies to treat severe measles. However, even if such treatments work, the best way to prevent the serious effects of measles is to avoid infection by getting vaccinated.The Conversation

Peter Kasson, Professor of Chemistry and Biomedical Engineering, Georgia Institute of Technology

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Supreme Court considers whether states may prevent people covered by Medicaid from choosing Planned Parenthood as their health care provider

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theconversation.com – Naomi Cahn, Professor of Law, University of Virginia – 2025-04-02 17:04:00

Planned Parenthood clinics, like this one in Los Angeles, are located across the United States.
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Naomi Cahn, University of Virginia and Sonia Suter, George Washington University

Having the freedom to choose your own health care provider is something many Americans take for granted. But the Supreme Court is weighing whether people who rely on Medicaid for their health insurance have that right, and if they do – is it enforceable by law?

That’s the key question at the heart of a case, Medina v. Planned Parenthood South Atlantic, that began during President Donald Trump’s first term in office.

“There’s a right, and the right is the right to choose your doctor,” said Justice Elena Kagan on April 2, 2025, during oral arguments on the case. John J. Bursch, the Alliance Defending Freedom lawyer who is representing South Carolina Director of Health and Human Services Eunice Medina, countered that none of the words in the underlying statute had what he called a “rights-creating pedigree.”

As law professors who teach courses about health and poverty law as well as reproductive justice, we think this case could affect access to health care for 72 million Americans, including low-income people and their children and people with disabilities.

Excluding Planned Parenthood

The case started with Julie Edwards, who is enrolled in Medicaid and lives in South Carolina. After she struggled to get contraceptive services, she was able to receive care from a Planned Parenthood South Atlantic clinic in Columbia, South Carolina.

Planned Parenthood, an array of nonprofits with roots that date back more than a century, is among the nation’s top providers of reproductive services. It operates two clinics in South Carolina, where Medicaid patients can get physical exams, cancer screenings, contraception and other services. It also provides same-day appointments and keeps long hours.

In July 2018, however, South Carolina Gov. Henry McMaster issued an executive order that barred health care providers in South Carolina that offer abortions from reimbursement through Medicaid.

That meant Planned Parenthood, a longtime target of conservatives’ ire, would no longer be reimbursed for any type of care for Medicaid patients, preventing Edwards from transferring all her gynecological care to that office as she had hoped to do.

Planned Parenthood and Edwards sued South Carolina, claiming that the state was violating the federal Medicare and Medicaid Act, which Congress passed in 1965, by not letting Edwards obtain care from the provider of her choice.

A ‘free-choice-of-provider’ requirement

Medicaid operates as a partnership between the federal government and the states. Congress passed the law that led to its creation based on its power under the Constitution’s spending clause, which allows Congress to subject federal funds to certain requirements.

Two years later, due to concerns that states were restricting which providers Medicaid recipients could choose, Congress added a “free-choice-of-provider” requirement to the program. It states that people enrolled in Medicaid “may obtain such assistance from any institution, agency, community pharmacy, or person, qualified to perform the service or services required.”

This provision is at the core of this case. At issue is whether a civil rights statute provides a right for Medicaid beneficiaries to sue a state when their federal rights have been violated. Known as Section 1983, it was enacted in 1871.

Bursch, backed by the Trump administration, argued before the court that the absence of words like “right” in the Medicaid provision that requires states to provide a free choice of provider means that neither Edwards nor Planned Parenthood has the authority to file a lawsuit to enforce this aspect of the Medicaid statute.

Nicole A. Saharsky, Planned Parenthood’s lawyer, argued that the creation of a right shouldn’t depend on “some kind of magic words test.” Instead, she said it was clear that the Medicaid statute created “a right to choose their own doctor” because “it’s mandatory” that the state provide this option to everyone with health insurance through Medicaid.

She also emphasized that Congress wanted to protect “an intensely personal right” to be able “to choose your doctor, the person that you see when you’re at your most vulnerable, facing … some of the most significant … challenges to your life and your health.”

Restricting Medicaid funds

Through a federal law known as the Hyde Amendment, Medicaid cannot reimburse health care providers for the cost of abortions, with a few exceptions: when a patient’s life is at risk or her pregnancy is due to rape or incest. Some states do cover abortion when their laws allow it, without using any federal funds.

Therefore, Planned Parenthood only gets federal Medicaid funds for abortions in those limited circumstances.

McMaster explained that he removed “abortion clinics,” including Planned Parenthood, from the South Carolina Medicaid Program because he didn’t want state funds to indirectly subsidize abortions.

South Carolina “decided that Planned Parenthood was unqualified for many reasons, chiefly because they’re the nation’s largest abortion provider,” Bursch told the Supreme Court.

But only 3% of Planned Parenthood’s services nationwide last year were related to abortion. Its most common service is testing for sexually transmitted diseases. Across the nation, Planned Parenthood provides health care to more than 2 million patients per year, most of whom have low incomes.

Man with gray hair in a suit and red tie speaks at a podium.
South Carolina Gov. Henry McMaster speaks to a crowd during an election night party on Nov. 3, 2020, in Columbia.
Photo by Sean Rayford/Getty Images

Section 1983

Because the Medicaid statute itself does not allow an individual to sue, Edwards and Planned Parenthood are relying on Section 1983.

Lower courts have repeatedly upheld that the Medicaid statute provides Edwards with the right to obtain Medicaid-funded health care at her local Planned Parenthood clinic.

And the Supreme Court has long recognized that Section 1983 protects an individual’s ability to sue when their rights under a federal statute have been violated.

In 2023, for example, the court found such a right under the Medicaid Nursing Home Reform Act. The court held that Section 1983 confers the right to sue when a statute’s provisions “unambiguously confer individual federal rights.”

Consequences beyond South Carolina

The court’s decision in the Medina case on whether Medicaid patients can choose their own health care provider could have consequences far beyond South Carolina. Arkansas, Missouri and Texas have already barred Planned Parenthood from getting reimbursed by Medicaid for any kind of health care. More states could follow suit.

In addition, given Planned Parenthood’s role in providing expansive contraceptive care, disqualifying it from Medicaid could harm access to health care and increase the already-high unintended pregnancy rate in America.

The ramifications, likewise, could extend beyond the finances of Planned Parenthood.

If the court rules in South Carolina’s favor, states could also try to exclude providers based on other characteristics, such as whether their employees belong to unions or if they provide their patients with gender-affirming care, further restricting patients’ choices.

Or, as Kagan observed, states could go the opposite direction and exclude providers that don’t provide abortions and so forth. What’s really at stake, she said, is whether a patient is “entitled to see” the provider they choose regardless of what their state happens to “think about contraception or abortion or gender transition treatment.”

If the Supreme Court rules that Edwards does have a right to get health care at a Planned Parenthood clinic, the controversy would not be over. The lower courts would then have to decide whether South Carolina appropriately removed Planned Parenthood from Medicaid as an “unqualified provider.”

And if the Supreme Court rules in favor of South Carolina, then Planned Parenthood could still sue South Carolina over its decision to find them to be unqualified.The Conversation

Naomi Cahn, Professor of Law, University of Virginia and Sonia Suter, Professor of Law, George Washington University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Feeling FOMO for something that’s not even fun? It’s not the event you’re missing, it’s the bonding

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theconversation.com – Jacqueline Rifkin, Assistant Professor of Marketing, Cornell University – 2025-04-02 07:48:00

They had so much fun without me.
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Jacqueline Rifkin, Cornell University; Barbara Kahn, University of Pennsylvania, and Cindy Chan, University of Toronto

Imagine you’ve planned the trip of a lifetime for your animal-loving family: a cruise to Antarctica with the unique opportunity to view penguins, whales and other rare wildlife. Your adventure-loving kids can kayak through fjords, plunge into icy water and camp under the Antarctic sky.

But rather than being ecstatic, as you anticipated, your kids whine about skipping an after-school scout meeting at a neighbor’s house. Missing this ordinary weekly event triggers such intense FOMO – “fear of missing out” – for them that they don’t want to go on your amazing expedition.

If this kind of debacle sounds familiar to you – or at least if you find it perplexing – you’re not alone. The three of us are marketing professors and social psychologists who focus on how consumers make decisions and how this shapes well-being. We’ve been studying FOMO for over a decade and recently published our work in the Journal of Personality and Social Psychology. Over the years, we’ve learned what really drives intense feelings of FOMO – which explains why a run-of-the-mill meeting might feel more crucial than an over-the-top vacation.

FOMO’s real trigger

People use the term FOMO in many different ways. In our research, we focus on a very specific type of FOMO: the kind that occurs when people miss out on events that involve valued social connections.

With this kind of FOMO, we found that the pain of missing out is not related to missing the actual event or opportunity – although that could be there as well. The FOMO we study happens when people miss the chance to bond with friends, co-workers or teammates they care about.

So, the critical part of FOMO is missing out on interactions with people you value. FOMO about a group dinner at a restaurant isn’t really about the food and great lighting. Nor is FOMO about a concert just about the band’s performance. Instead, it’s about the lost opportunity to connect and make memories with people who are important to you.

Why is this upsetting? Imagine the scenario where all your best friends go out to dinner without you. They bond and make lasting memories with each other – and you’re not there for any of it.

If they get closer to each other, where does that leave you? What happens to your social relationships and your sense of belonging? Do you become a less important friend? Less worthy of future invites? Or even kicked out of the group altogether? The anxiety of FOMO can begin to spiral.

People with what psychologists call an anxious attachment style chronically fear rejection and isolation from others. Because FOMO involves anxiety about future social belonging, it may not come as a surprise that people who are naturally more anxious about their friendships tend to get more intense FOMO. When we asked people in one of our studies to scroll social media until they encountered something social they missed, we found that the more anxiously attached a participant was, the more intense FOMO they experienced.

cheerful group laughing together around an outdoor dining table
They’ll always remember that summer cookout – and you weren’t there.
Maskot/DigitalVision via Getty Images

Not just missing Coachella

Getting FOMO for an amazing event you can’t attend makes sense. But if FOMO is less about the event itself and more about the social bonding, what happens when you miss something that’s not really fun at all?

We find that people anticipate FOMO even for unenjoyable missed events. As long as there is some form of missed social bonding, feelings of FOMO emerge. One of our studies found that people anticipated more FOMO from missing an un-fun event that their friends would be at, than a fun event without their friends.

For better or for worse, sad and stressful events can often be emotionally bonding: Going to a funeral to support a friend, cleaning up the mess after a party, or even white-knuckling through a harrowing initiation ceremony can all offer opportunities to forge stronger connections with one another. Stressful contexts like these can be fertile grounds for FOMO.

How to fend off FOMO

Popular discussions about the negative consequences of FOMO tend to focus on the FOMO people feel from compulsively scrolling on social media and seeing what they missed out on. Consequently, much of the suggested advice on how to mitigate FOMO centers on turning off phones or taking a vacation from social media.

Those recommendations may be tough for many people to execute. Plus, they address the symptoms of FOMO, not the cause.

Our finding that the core of FOMO is anxiety about missed social relationships yields a simpler strategy to combat it: Reminding yourself of the last time you connected with close friends may provide a sense of security that staves off feelings of FOMO.

In an experiment testing multiple interventions, we asked 788 study participants to look through their social media feeds until they encountered a post of a missed social event. We asked about 200 of these participants to immediately rate how much FOMO they were feeling. They averaged a 3.2 on a 1-to-7 scale.

Another group of about 200 participants also scrolled through their social media feeds until they encountered a post of a missed social event. But before indicating how much FOMO they were feeling, we asked them to think back to a prior experience socializing and bonding with their friends. Encouragingly, this reflection exercise seemed to curtail FOMO. Their average FOMO rating was 2.7 out of 7, a significant drop.

group of older women on a neighborhood walk with a leashed dog
Reminding yourself about other good times with your pals can help keep FOMO at bay.
AJ_Watt/E+ via Getty Images

With the remaining participants, we tested other strategies for mitigating FOMO – thinking about the next time they might see their friends or imagining what they’d say to a FOMO-suffering friend – but the simple reflection exercise was by far the most promising.

So, reminding yourself of the meaningful relationships you already have and reaffirming your social belonging in the moment may help combat the rush of anxiety that is characteristic of FOMO.

And missing out on social bonding experiences doesn’t have to be anxiety-provoking. In fact, in our activity-packed, hectic lives, missing some “must-attend” events may be a welcome relief – especially if you remind yourself that your social belonging is not in jeopardy. Cue a recent wave of counter-FOMO programming called JOMO, or “Joy of Missing Out.”

To quote Stuart Smalley, the fictional self-help guru of 1990s “Saturday Night Live,” reminding yourself that “I’m good enough, I’m smart enough, and doggone it, people like me!” might be just the trick to mitigate FOMO.The Conversation

Jacqueline Rifkin, Assistant Professor of Marketing, Cornell University; Barbara Kahn, Patty and Jay H. Baker Professor of Marketing, University of Pennsylvania, and Cindy Chan, Assistant Professor of Marketing, University of Toronto

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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