Vaccines, Advances in Medicine Li-Anne Rowswell Mufson Vaccines, Advances in Medicine Li-Anne Rowswell Mufson

Background of the Breakthroughs of mRNA

By Michael Bronfman, June 23, 2025

Dr. Katalin Kariko, Nobel Prize winning scientist, mRNA vaccine pioneer

This week, The Guard Rail is diving into a topic that has truly revolutionized modern medicine: Messenger RNA, or mRNA. What was once merely a fascinating concept in biology has rapidly become a groundbreaking platform, and its incredible success in the COVID-19 vaccine development is just the beginning. Join us as we explore the captivating scientific journey of mRNA, highlighting the decades of innovation in molecular biology, chemistry, and nanotechnology that led to its triumph. We will also spotlight the key innovators who made it all possible, with a special nod to the remarkable influence of Dr. Katalin Karikó and Dr. Drew Weissman and peek into the exciting future promise of mRNA-based therapeutics.


The Arrival of a New Therapeutic Frontier

Messenger RNA (mRNA) has rapidly transitioned from a biological curiosity to a revolutionary platform in medicine. Its recent triumph—vaccine success against COVID-19—stemmed from decades of incremental yet transformative molecular biology, chemistry, and nanotechnology breakthroughs.


1. From Molecular Discovery to Therapeutic Aspiration

  • 1961 – mRNA Identified

Scientists first recognized mRNA as the key intermediary transmitting genetic information from DNA to ribosomes. This discovery laid the molecular foundation for engineering mRNA for therapeutic use.

  • 1990 – Synthetic mRNA Demonstrated

Jon A. Wolff and colleagues injected synthetic mRNA into mouse muscle, successfully producing proteins in vivo—an early hint at mRNA's therapeutic potential. See: time.com+3penntoday.upenn.edu+3science.org+3en.wikipedia.org+4en.wikipedia.org+4en.wikipedia.org+4.

Despite the promise, these pioneering experiments raised fundamental obstacles: mRNA's inherent fragility, strong immunogenicity, and inefficient cellular delivery.

2. Cracking the Code: Reducing Immunogenicity via Nucleoside Modification

  • 1997–1998 – The Penn Collaboration Begins
    At the University of Pennsylvania, biochemist Katalin Karikó and immunologist Drew Weissman formed a partnership driven by a shared interest in harnessing mRNA. See: nature.com+15bu.edu+15teenvogue.com+15.

  • 2005 – Seminal Discovery

    They revealed that unmodified synthetic mRNA activates Toll‑like receptors in dendritic cells, triggering inflammation. Crucially, swapping out uridine with pseudouridine (or other modified nucleosides) dramatically suppressed this response, mitigating immunogenicity and enhancing protein translation. See: jbiomedsci.biomedcentral.com+15nobelprize.org+15jci.org+15.


These findings marked a watershed—chemical modification of mRNA transformed it into a viable therapeutic candidate, earning the duo the 2023 Nobel Prize in Physiology or Medicine. See: en.wikipedia.org+3time.com+3nobelprize.org+3

3. Packaging Success: Lipid Nanoparticles Enable Delivery

  • Development of mRNA-LNP Systems

    Research in the late 2000s and 2010s refined LNP formulations tailored to shield mRNA from degradation, enable cellular entry, and facilitate efficient endosomal escape. See: mdpi.compubs.rsc.org.

Notable innovations include ionizable lipids, helper lipids, cholesterol, and PEGylated lipids, collectively optimizing pharmacokinetics, stability, and safety. See: mdpi.com.

  • Clinical Translation

    This chemistry and engineering synergy culminated in the approval and deployment of the first lipid nanoparticle-based mRNA vaccines during the COVID-19 pandemic.

4. Pre-Pandemic Explorations

Even before 2020, mRNA therapeutics were under active development:

  • Cancer Vaccines: Preclinical and early clinical trials featured mRNA encoding tumor-specific antigens delivered via LNPs to prime anti‑tumor immunity.

  • Infectious Disease Vaccines: mRNA vaccines targeting rabies, Zika, influenza, and HIV entered early human trials, demonstrating both feasibility and promise. See: arxiv.org+3teenvogue.com+3wired.com+3.

  • Protein Replacement and Gene Editing: Applications using LNP-delivered mRNA for protein replacement therapies and CRISPR editing emerged in preclinical stages. See: mdpi.com+2pmc.ncbi.nlm.nih.gov+2pubs.rsc.org+2.

  • Pioneering Companies: Moderna (founded 2010) and BioNTech (2008) both built platforms centered on Karikó/Weissman technology and LNPs. BioNTech later partnered with Pfizer to develop its COVID-19 vaccine regimen.

5. The COVID‑19 Catalyst & Rapid Deployment

When SARS-CoV‑2 emerged in early 2020, the platform's modular nature and advanced formulations enabled unprecedented speed:

  • Clinical Trials: Moderna began human trials in March 2020. By December, both mRNA‑1273 (Moderna) and BNT162b2 (Pfizer‑BioNTech) secured Emergency Use Authorization based on ~95% efficacy. See: nature.com.

This success validated decades of incremental innovation: nucleoside-modified mRNA + optimized LNPs = real-world impact.

6. Recognition: The Nobel and Beyond

The scientific community honored Karikó and Weissman's pivotal contributions:

7. Beyond Vaccination: Broadening the mRNA Horizon

The mRNA platform's adaptability has ignited diverse research avenues:

  • Cancer Therapies: Personalized mRNA vaccines targeting neoantigens, mRNA‑encoded cytokines, and CAR-T therapies are progressing in clinical evaluation.

  • Gene Editing & Protein Replacement: mRNA-driven CRISPR approaches for in vivo editing, and LNP-encoded enzyme replacement therapies (e.g., for genetic disorders) are expanding mdpi.com+1jbiomedsci.biomedcentral.com+1.

  • Autoimmunity & Regenerative Medicine: Early-stage efforts are exploring mRNA-induced immune tolerance and tissue regeneration applications.


8. Continued Innovation & Challenges

Despite remarkable success, key areas require continued innovation:

  • Delivery Precision: Next-gen LNPs (e.g., organ-selective or SORT nanoparticles) aim to enable tissue-specific targeting beyond the liver en.wikipedia.org+1arxiv.org+1.

  • Stability & Design Optimization: Advanced methods like codon optimization and structure-prediction algorithms (e.g., LinearDesign) enhance mRNA stability and translational efficiency arxiv.org.

  • Manufacturing Scale & Supply: Scaling up mRNA and LNP production, maintaining cold chain logistics, and ensuring global access remain formidable obstacles wired.com+1mdpi.com+1.

  • Safety & Regulation: Comprehensive long-term safety monitoring—especially with novel ionizable lipids and repeated dosing—is critical pmc.ncbi.nlm.nih.gov.

  • Cost & Accessibility: Ensuring equitable pricing and widespread distribution, especially to low- and middle-income countries, remains essential.

9. Timeline of Key Milestones

Year Breakthrough

1961 Discovery of mRNA

1990 Synthetic mRNA expression in mice

1997–98 Karikó & Weissman collaboration begins

2005 Pseudouridine‑modified mRNA suppresses immune activation

2018 FDA approves LNP‑siRNA therapy Onpattro

2020 First mRNA COVID‑19 vaccine trials and rollout

2023 Nobel Prize for Karikó & Weissman

10. In Conclusion: A Platform Reborn

The mRNA story is a testament to scientific persistence, collaboration, and cumulative innovation. From a molecular curiosity to a global vaccine solution, the ascent of mRNA illustrates how challenges—fragility, immunogenicity, delivery—were methodically overcome with modified nucleosides and precision lipid carriers.

The result? A modular, adaptable therapeutic platform poised to revolutionize vaccines, cancer therapy, gene editing, and more. Let this narrative serve both as a chronicle of what has been achieved and a roadmap for what's next in the pharma world.

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Don't leave your innovative drug development projects to chance. Let Metis Consulting Services help to leverage unparalleled expertise in navigating the intricate pathways of pharmaceutical research and development. We provide comprehensive guidance, from early-stage discovery to clinical translation, ensuring your projects are optimized for success.

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Be sure to check out our podcast, Queens of Quality for more informative and interesting conversations about this and more bio/pharma hot topics.

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Autism Spectrum Disorder Li-Anne Rowswell Mufson Autism Spectrum Disorder Li-Anne Rowswell Mufson

What Autism is Not

If you work in pharma or medtech, chances are you’ve come across some of the misconceptions that still swirl around Autism Spectrum Disorder (ASD). Despite decades of scientific research, myths continue to muddy the waters. At the top of that list? The long-debunked idea that vaccines cause autism. (Spoiler alert: They don’t. Not even a little.)

By Michael Bronfman, May 21, 2025

Author assisted by AI

What autism is not

Welcome back to our second article in our unmet needs series: Autism

In our Last post we explored what exactly autism is and this week, we are looking into “What Autism is Not.”

Understanding What Autism Isn’t Caused By

Debunking the Vaccine Myth and Other Common Misconceptions

Let’s talk about autism—but more specifically, let’s talk about what doesn’t cause it.

If you work in pharma or medtech, chances are you’ve come across some of the misconceptions that still swirl around Autism Spectrum Disorder (ASD). Despite decades of scientific research, myths continue to muddy the waters. At the top of that list? The long-debunked idea that vaccines cause autism. (Spoiler alert: They don’t. Not even a little.)

And while we’re at it, let’s also clear the air on some other outdated beliefs, like blaming screen time, parenting, or gluten. Let’s cut through the noise with facts and help our industry—and the broader public—move forward with a more accurate understanding of the autism spectrum.



Let’s Start with the Big One: Vaccines

The vaccine-autism myth started back in 1998 with a now-infamous study published in The Lancet. A British doctor named Andrew Wakefield claimed that the MMR (measles, mumps, rubella) vaccine was linked to autism. The paper had a grand total of 12 participants. 1 That’s not a typo—just twelve.

The media ran with it. Fear spread like wildfire. Vaccination rates dropped. Measles came roaring back. But here’s the thing:

The study was flawed, unethical, and ultimately fraudulent.

Wakefield’s medical license was revoked. The Lancet retracted the paper.2 And since then, numerous large-scale studies—we’re talking hundreds of thousands of kids—have found no link between vaccines and autism. One of the biggest, a 2019 Danish study, looked at over 650,000 children. Still no connection.3

So why does this myth still have legs? Fear is powerful. But facts are more powerful—if we keep pushing them forward.

Other Things That Don’t Cause Autism

Beyond vaccines, autism has been blamed on a laundry list of things. Let’s bust a few more myths:

1. Parenting Style

Remember the “refrigerator mother” theory from the mid-20th century? The idea that cold or unloving mothers caused autism? Total bunk. It’s not your parenting. Autism has strong genetic roots, not emotional ones.4

2. Trauma or Stress

No, trauma doesn’t cause autism either. Stress can affect development in various ways—but it doesn’t explain the neurological differences we see in autistic individuals.5

3. Screen Time

The potential link between screen time and autism has been the subject of numerous studies in recent years. While some research has suggested a correlation between increased screen time and autism-like behaviors, it’s crucial to approach these findings with caution and understand their limitations. For example a review of multiple studies published 2019-2023 was published in the Journal of the American Medical Association (JAMA) Pediatrics. They found that children who spent more time watching screens at age 1 year showed more autism-like symptoms at age 2 years. However, the researchers emphasized that this association does not prove causation and that more research is needed to understand the relationship fully.6

So What Does Contribute to Autism?

While there’s still a lot to learn, we know a few things for sure:

1. Genetics

Autism is highly heritable. Twin studies and genome research have identified hundreds of genes involved in brain development that are linked to ASD. It’s complex, but genetics play a major role.

2. Prenatal Factors

Some prenatal conditions—like parental age-for example, if the father is over age 40- complications during pregnancy, or certain environmental exposures—may increase the risk of autism in genetically susceptible individuals. But these are risk factors, not causes.

The “Spectrum” in Autism Spectrum Disorder

One of the most important things to understand about autism is that it isn’t a one-size-fits-all condition. That’s why it’s called a spectrum.

Some individuals might need 24/7 support. Others might be independent professionals in STEM fields. The diversity across communication styles, social behavior, interests, and sensory experiences is vast.

Here are a few key areas where the spectrum really shows up:

Communication: Some are non-verbal. Others are eloquent but struggle with back-and-forth conversation or reading social cues.

Social Interaction: Some prefer solitude, others crave connection but find social settings overwhelming.

Repetitive Behaviors: From stimming (like hand-flapping) to intense focus on niche topics—these behaviors vary in type and impact.

Sensory Processing: Lights, sounds, textures—what feels normal to one person might be unbearable or barely noticeable to someone on the spectrum.

This variability is exactly why the DSM-5 consolidated various subtypes into one diagnosis—Autism Spectrum Disorder—in 2013.7

Why This Matters in Pharma and Medtech

Whether you’re developing therapies, diagnostics, or digital health tools, understanding the true nature of autism helps you better serve a highly diverse and underserved population. It also helps ensure you don’t inadvertently perpetuate myths through marketing, trial design, or stakeholder education.

Especially in smaller companies, where agility and mission-driven work are your superpowers, there’s a unique opportunity to lead with empathy and science.

Final Thought: Stick to the Science

It’s easy to get caught up in popular narratives, but in healthcare, we have a responsibility to fight misinformation—especially when it leads to public health risks, like vaccine hesitancy.

Autism is not caused by vaccines. Or screen time. Or poor parenting. It’s a neurodevelopmental condition with a genetic backbone and a complex presentation that varies from person to person.

If we want to build a more informed, compassionate world—not to mention better products and services for the autism community—we’ve got to start by ditching the myths and doubling down on the facts.



Want to help reshape how your company talks about autism? Please contact us at Metis Consulting Services. We are  here for it. Let’s raise the bar together.

1. https://publichealth.jhu.edu/2025/the-evidence-on-vaccines-and-autism

2. https://pubmed.ncbi.nlm.nih.gov/12421889/

3. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(04)16017-0/fulltext

4. https://neurolaunch.com/refrigerator-mothers/

5. https://pmc.ncbi.nlm.nih.gov/articles/PMC6901292/ 

6. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2812722  

7.  https://rxpin.com/2025/02/27/the-evolution-of-autism-diagnosis-from-dsm-iv-to-dsm-5/ 

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