Radically different
Nature Biotechnology, Published online: 11 May 2026; doi:10.1038/s41587-026-03155-8
While circRNA is often framed as a more stable, longer-lasting alternative to linear mRNA, its real-world advantages remain largely theoretical, and it is unclear whether greater molecular stability will translate into meaningful clinical gains.
The rapid growth of cell and gene therapies is exposing structural limitations in how traditional biopharmaceutical systems were designed. Unlike batch-based manufacturing models, these therapies are patient-specific, requiring tightly coordinated execution across clinical, manufacturing, and quality domains.
In this environment, maintaining chain-of-identity and chain-of-custody is not simply a regulatory requirement, but a foundational design constraint. As programs move from early clinical development into global commercialization, gaps in system-level orchestration can translate directly into compliance and operational risk.
These pressures are driving renewed attention toward how digital infrastructure is architected in regulated life sciences, particularly around validation, traceability, and cross-system integration.
Monika Birdi, global product strategy leader for SAP’s Cell and Gene Therapy Orchestration (CGTO) platform, has spent more than two decades working on regulated enterprise systems across industries, with a recent focus on advanced therapy manufacturing and supply chains. In this interview with GEN, Birdi discusses SAP CGTO’s architecture, regulatory design in SAP Batch Release Hub (BRH) and Intelligent Clinical Supply Management (ICSM), and digital frameworks for inspection readiness, jurisdictional control, and chain-of-identity enforcement. She also shares insights on balancing innovation with GxP validation and building digital infrastructure for global commercialization of patient-specific therapies.
GEN: What foundational lessons about compliance architecture, data integrity, and large-scale system design most influenced your transition into life sciences and cell and gene therapy?
MB: The biggest shift I experienced after moving to life sciences was in perspective and significance. During the many years I worked building large-scale regulated systems in diverse industries, a failure of data integrity meant financial loss or reputational damage. However, when I moved into the pharma and biotech life science sectors, I realized that in this domain, there was zero margin for error. If the chain-identity breaks anywhere in that journey, there is no fallback.
This reality puts compliance at the heart of architecture. Controls need to be built from the start and cannot be retrofitted later. We must stop treating compliance and scalability as competing priorities, because when you architect them together, one enables the other.
GEN: When you began working in advanced therapies, what operational or digital fragilities did you observe in early-stage programs that signaled a structural gap in how regulated supply chains were being architected?
MB: The first thing we need to understand is that advanced therapies are completely different from traditional small molecule manufacturing. Hence, for organizations that have been in the pharma business, shifting to manufacture advanced therapies is different from both scientific and architectural perspectives. The same tools that worked for small molecules will not serve the end-to-end business for advanced therapies.
The common structural gaps I observed were around chain of identity and chain of custody tracking. Since these are typically not part of the native system design, every single process runs via piles of papers that are difficult to organize and trace. In these cases, there was no orchestration layer and all the systems—such as clinical, manufacturing, quality—were running in silos.
GEN: You have led the design and commercialization of SAP CGTO. What operational failures or regulatory risks did you observe in early-stage CGT programs that convinced you digital orchestration had to be architected differently from traditional pharma systems?
MB: Traditional pharma systems are built around batch manufacturing, where thousands of units are manufactured in one batch. Even if one batch fails the compliance, the next batch can be used by discarding the non-compliant batch. Chain-of-identity is being maintained through a combination of spreadsheets. This is what convinced me to rethink orchestration. You can’t take a traditional batch management system and configure your way into CGT compliance.
The right therapy needs to reach the right patient. So, with CGTO, the design question was never “how do we adapt existing functionality” to make a compliant solution. Our approach was to ask, “if we are building this from scratch for one patient and one batch, what should the process actually look like?”
GEN: Autologous cell and gene therapy manufacturing is patient-specific and tightly synchronized. How did you architect SAP CGTO to enforce chain-of-identity and chain-of-custody controls at every transition point rather than relying on retrospective reconciliation?
MB: Personalized advanced therapies operate under a unique manufacturing cycle, which makes conventional post-production reconciliation processes ineffective. We needed an architecture that shifts the control point from “detect and correct” to “prevent and confirm” for every transaction.
With SAP CGTO, every transition point, from receipt at the plant, disposition, manufacturing start, and allocation to final shipment, is within an order and includes validations to make sure the right patient gets the right therapy. The system won’t let you proceed with a mismatched identity. These validations ensure that the process is stopped immediately, instead of alerting the user at a later point in time.
GEN: In your work on SAP BRH, you focused on jurisdiction control and regulatory components. How do digital release architectures need to evolve to support multi-country regulatory environments while preserving data integrity and inspection readiness?
MB: Most organizations use local Standard Operating Procedures (SOPs) and spreadsheets, utilized by people who have been around long enough to manage the regulatory requirements. This system will likely fail if a critical employee leaves, or if you are entering a new market under pressure, or when an inspector asks you to reconstruct a release decision from two years ago.
Jurisdictional controls should be part of the solution. Once validations are embedded directly into workflows, compliance becomes part of the business process. The audit trails are thus automatically created as a natural result of doing the job.
GEN: You believe designing infrastructure before scale exposes operational gaps. What are the most common digital fragilities you see when sponsors defer enterprise architecture decisions until Phase III or Phase IV?
MB: In cell and gene therapy, many sponsors treat digital infrastructure like office furniture: something to worry about later. The largest problems tend to be in two areas: traceability and coordination.
In terms of traceability, it’s common for programs to track materials in whatever way is convenient at that time, such as spreadsheets, half-set-up software, or systems that don’t talk to one another. But for a hundred patients across many sites, it becomes nearly impossible to track it all correctly, especially when the FDA starts asking questions.
But as trials get bigger, it becomes difficult to manage all of it through those means—and in fact, it can become dangerous. Then, as the trial advances, scale your investment in alignment with emerging trial results.
GEN: Across CGTO, BRH, and ICSM, you have helped define regulatory-ready digital architectures for emerging therapy models. What measurable operational or compliance outcomes have resulted from these implementations, and how do they demonstrate advancement in the field’s digital maturity?
MB: The actual benefit of digitalization in advanced therapies shows up in audits and inspections. By ensuring that digital systems are properly implemented from the beginning and integrated with quality and batch record systems, decisions regarding the release of batches are much faster and more accurate.
In the area of clinical trials, integrated systems enable teams to predict and prevent problems rather than simply reacting to them. This results in fewer delays, and the benefits are easy to demonstrate and prove to the authorities.
GEN: What principles guide your approach to building compliant cloud-native platforms that remain modular, secure, and extensible?
MB: I believe modularity itself is a compliance strategy. Highly integrated platforms introduce hidden risk, because every regulatory change or market requirement can trigger system‑wide retesting.
I design security and extensibility together, with clear separation between what is validated, configurable, and subject to formal change control. That clarity allows teams to move faster without compromising compliance.
Commercialization teaches you that adoption depends on validation of reality. A platform can be technically strong, but if it is difficult to validate and operate in a regulated environment, it will not be scaled. The most successful products do not transfer the customer’s validation burden.
GEN: As advanced therapy pipelines expand and manufacturing networks become more geographically distributed, which architectural capabilities will determine whether organizations can sustain compliant commercialization without repeated remediation cycles?
MB: We need to start building compliance as the core of architecture instead of treating it as per each unique market need. Once the foundation has been set, market regulations can be adjusted accordingly. A few capabilities in which I would invest early include real-time chain-of-identity enforcement, jurisdictional logic embedded in workflows rather than documented beside them, and audit structures that generate inspection-ready data as a natural output, as opposed to a reconstruction exercise. What really matters most is the flexibility of architecture. Regulations evolve, new markets pop up, and manufacturing networks constantly adapt and relocate. This requires organizations to build adaptable and modular architecture that can evolve with growth.
The post How Digital Orchestration Is Redefining Regulatory Infrastructure for Cell and Gene Therapy appeared first on GEN – Genetic Engineering and Biotechnology News.
J. Craig Venter, PhD recently passed away at the age of 79 from complications following a cancer diagnosis. He was well known in both science and industry and was an integral part of sequencing the human genome in the late 90s, competing with the government organized Human Genome Project. Throughout his career, he made many other important contributions in microbiology, with the “minimal cell,” in synthetic biology, and in personalized medicine. GEN editors share anecdotes of their experiences with him, reflect on the impact that his work has had on various fields in biology, in biotech, and in how the world has responded to the disruptions caused by Venter.
Listed below are links to the GEN stories referenced in this episode of Touching Base:
Genomics Pioneer and Life Sciences Entrepreneur J. Craig Venter Dies at 79
GEN, April 30, 2026
J. Craig Venter Describes a Human Genomics Revolution Still In Progress
By J. Craig Venter, PhD, GEN, June 13, 2025
Lessons from the Minimal Cell
By Hana El-Samad, PhD, GEN, August 21, 2023
From Sequencing to Sailing: Three Decades of Adventure with Craig Venter
By Fay Lin, PhD, GEN, March 8, 2023
“Cracking the Genome”
By Kevin Davies, PhD
Touching Base Podcast
Hosted by Corinna Singleman, PhD
Behind the Breakthroughs
Hosted by Jonathan D. Grinstein, PhD
The post Remembering J. Craig Venter, PhD appeared first on GEN – Genetic Engineering and Biotechnology News.
The 29th American Society of Gene & Cell Therapy (ASGCT) meeting kicks off in Boston next week. The annual event will be a whirlwind of sessions, keynotes, fireside chats, posters, and exhibitors.
For the second year in a row, GEN spoke with David Barrett, JD, who has been the CEO of ASGCT since 2016. In this interview, we discuss his perspective on the event, if there is anything new that attendees should be looking out for, and what he, personally, is most looking forward to.
This interview has been edited for length and clarity.
LeMieux: The ASGCT meeting is an annual event. What are some of the things that will make this year’s meeting special?
Barrett: There is a lot that is special this year. First and foremost, it feels like a bit of a homecoming which is really exciting. The last time we were in Boston was in 2008. And Boston is a city and community where gene therapy, biotech, and research are all located. You can feel it when you’re in Cambridge and I think you are absolutely going to feel that when you’re inside the convention center.
The fact that the meeting is in Boston this year is also special for me because one of the very first things I did when I joined ASGCT in 2016, was to source the location for the 2020 annual meeting at the Hynes Convention Center in Boston. I was very excited and it was the first time we were going to take up an entire convention center. But that meeting, of course, did not happen; it had to be canceled because of COVID. So that makes this meeting in Boston particularly special. We finally get to have the meeting in Boston that I’ve been hoping for since 2016!
And we are growing. We are at the bigger of the two convention centers in Boston. We are going to surpass the total number of people that we had last year and I have every expectation that we’ll see significant growth year over year.
As far as other things that are that are new and interesting this year… I said this last year, but it’s worth adding it again—the science is always different. It is very consistent that we will have great science every year, and it is a wonderfully fun question mark of what exactly that science is going to look like. It’s always exciting because the science is always different year after year. So, by its very nature, it will be an exciting new conference this year.
Also, we’ll have a puppy park in the exhibit hall, so that’s really fun!
LeMieux: What are some things that will be highlighted at the meeting that ASGCT has been working on over the past year?
Barrett: ASGCT has done a lot this year. There is a lot that we have been very vocal about so far, and there is a lot that we’ll be sharing during the annual meeting.
Number one is that we partnered with Orphan Therapeutics Accelerator (OTXL) to found CGTxchange—the first and only clearing house and marketplace of its kind for cell and gene therapy assets. It is being built as we speak and we’ll have some exciting announcements during the annual meeting about assets that will hopefully be in the CGTxchange by that point. It is the culmination of a lot of work on what to do about commercially pre-viable (not non-viable) cell and gene therapies and the work that we’re doing to make those more commercially possible.
Also, ASGCT is hosting its Momentum Gala—the first formal gala at our annual meeting. That event has resonated really well with sponsors and donors. In fact, it is sold out! That event is going to be used to celebrate the launch of ASGCT Foundation, which is a separately incorporated 501C3 charitable foundation to support ASGCT’s mission to advance early career researchers and enable the development of cell and gene therapies. Also at the gala, we’ll be announcing some new initiatives to support patient access and reduce barriers to diagnosis, clinical trial participation, and treatment with cell and gene therapies.
Another major thing that’s going on is a considerable expansion of our educational activities. We recently launched a new e-learning tool and platform—the ASGCT Learning Center—a really fun project that we’ve been working on to expand how we we are getting new content to our new and expanding audiences.
We recognize that we have a really broad audience at ASGCT that is made up of cell and gene therapy basic science researchers, translational researchers, physician scientists and others in the ecosystem of drug development and administration for cell and gene therapies. And we’re looking at new ways to provide content that can help satisfy the learning needs of that really broad audience. The learning center is a big tool in our quiver to be able to do that.
LeMieux: What do you hope people take away from the meeting?
Barrett: I hope they take away a couple of things… number one, I hope they take knowledge, education, and awareness of what’s going on in the space and what has been happening over the course of the last 12 months. I hope that they take that back to their individual place of work. And I hope that, generally speaking, we fulfill our mission by expanding that knowledge base among all of the stakeholders in cell and gene therapy. Another thing that I hope people take away from this is that, after a lot of ups and downs and undulations in this field over the course of the past two to three years, that there is an extraordinary sense of excitement about the next phases in the development of cell and gene therapy drugs.
We have some really exciting new regulatory pathways. We have a lot of development of personalized gene editing technologies and techniques that can bring gene therapies much more quickly and effectively to patients who need them. We have seen significant advancements in more traditional or classic AAV gene therapies that are allowing these to be safer and more efficacious. And we’re seeing an expansion of cell-based gene therapies through an ever-expanding portfolio of indications that are reached by CAR Ts, primarily in cancer, but in an expanding outlook for the use of CAR Ts outside of cancer as well. So, I am hopeful that attendees come away with a renewed energy and vigor for the development of satellite gene therapies.
LeMieux: Is there anything specific planned at the meeting to touch on the concerns of the challenges that the scientific community is facing right now—with funding or other barriers?
Barrett: We are very excited to have Katherine Szarama, PhD—who was recently named acting director of FDA’s Center for Biologics Evaluation and Research (CBER)—participating in a fireside chat, addressing regulatory uncertainties. [Szarama replaced Vinay Prasad, MD, MPH, on May 1st.]
We have two other fireside chats focused on regulation, as well. The three fireside chats will offer attendees an opportunity to learn a little more, ask some questions, and hear from some of the individuals in those sessions specifically.
But I think that people will also see, more broadly, the ongoing work that ASGCT is doing to continue to create a partnership and a positive working relationship with the FDA to support those regulatory concerns.
LeMieux: What are you most looking forward to?
Barrett: I think I said this last year, but it really is one of my favorite components of the annual meeting. Every year, I look forward to taking some time to watch the exhibit hall being built. When the rope drops and people enter the exhibit hall for that very first reception, the hall is in pristine condition. And one of my favorite parts is watching it get to that pristine condition because it is just so exciting to see everything being built and come to a head, to have the whole field enter all at one space, and to be able to see an industry live and in person. Because so much of what we do is at our computer screens—and what we read about, hear about, or listen to people talk about. But when you actually see the field of gene and cell therapy on display, it is really exciting and satisfying.
Lastly, I will add that I’m looking forward to eating too much clam chowder while in Boston (chuckling).
The post ASGCT CEO David Barrett Previews the Upcoming Conference in Boston appeared first on GEN – Genetic Engineering and Biotechnology News.
Biotechnology company ParcelBio said this week that it has raised $13 million in a seed financing round led by Breyer Capital with participation from General Catalyst, Y Combinator, Metaplanet, SurgePoint Capital, ZAKA VC, and other investors. The financing will support the development of the company’s proprietary Amplified and Prolonged EXpression mRNA (APEXm
) platform and advance its pipeline including an in vivo CAR T program for autoimmune disease, as well as additional programs in oncology and encoded protein therapeutics.
The company, which is developing what it describes as a new class of durable mRNA medicines, will debut APEXm and share some preclinical data at the American Society of Gene and Cell Therapy annual meeting. This year’s meeting is being held in Boston, Massachusetts and will run from May 11-15. The company claims that its data will demonstrate that ParcelBio’s APEXm RNA drives significantly higher and more durable protein expression compared to another clinical mRNA design, and yields more complete target cell depletion in in vivo CAR T models.
“mRNA has transformed medicine, but today’s technologies are fundamentally limited in how much protein they can produce and for how long,” said David Weinberg, PhD, chief executive officer and co-founder of ParcelBio. His company’s proprietary technology addresses this problem by engineering RNA molecules to recruit the cell’s native RNA-stabilizing machinery, which enables higher and more durable protein expression. The company claims that its approach will result in medicines that reach thresholds that have historically been challenging for mRNA-based therapeutics. “We engineered RNA to work with the cell’s machinery rather than against it, enabling meaningful improvements in both expression and durability that we believe are essential for true disease modification,” Weinberg said.
Furthermore, ParcelBio’s platform maintains a simple, linear RNA architecture unlike circular RNA and other approaches, whose structure introduces manufacturing complexity or reduces output. Its broad applicability across proteins and cell types makes it suited for various therapeutic applications including immune programming and protein replacement.
“Most RNA platforms force a tradeoff between potency, durability, and manufacturability,” said Chris Carlson, PhD, chief scientific officer and co-founder of ParcelBio. “Our approach eliminates that tradeoff, enabling both higher peak expression and longer duration within a manufacturable system, and opening the door to entirely new classes of medicines.”
ParcelBio’s lead program focuses on in vivo CAR T therapies that target pathogenic B cells across autoimmune diseases, with the goal of achieving deep B-cell depletion for durable, drug-free remission. By enabling sustained CAR expression without viral delivery or ex vivo manufacturing, the company aims to develop scalable, off-the-shelf therapies. Additional programs leveraging the technology are currently in development in oncology and encoded protein therapeutics.
The post ParcelBio Unveils Programmable mRNA Platform Backed by $13M Financing appeared first on GEN – Genetic Engineering and Biotechnology News.
This is today’s edition of The Download, our weekday newsletter that provides a daily dose of what’s going on in the world of technology.
AI is spreading everywhere, and it is not going away. But what will it do? What effect will it have on our society? Will it make life better, or worse? How will we know? What’s the plan?
This technology may very well take our jobs—or just crash the economy instead. Our apps are all getting injections of AI, like it or not. And it is increasingly impossible to tell whether we are relying too much on AI or not using it enough.
We’re all sitting uncomfortably with AI right now. Read our essay on the strange, uncertain mood of the moment.
The era of AI malaise is an essay written by our editor-in-chief Mat Honan. It accompanies MIT Technology Review’s 10 Things That Matter in AI Right Now, our list of the big ideas, trends, and advances in the field that are driving progress today—and will shape what’s possible tomorrow.
Technology is changing the way we make babies. Clinicians have improved hormonal treatments. Embryologists have devised ways to culture embryos in the lab for longer. IVF clinics today offer multiple genetic tests for embryos.
The technology has also had a huge social impact, allowing for changes in the structure of families and providing more reproductive choices for would-be parents. Now, AI and robots are set to usher in another new era for IVF.
Here’s how technology is reshaping babymaking.
—Jessica Hamzelou
This story is from The Checkup, our weekly newsletter giving you the inside track on all things biotech. Sign up to receive it in your inbox every Thursday.
For decades, researchers have been inspired by science fiction robots that can move through the world, adapt to different environments, and interact with people. But bringing these devices into the messiness of the real world has proved incredibly difficult.
Now, advances in AI are changing that. Instead of relying on rigid rules, robots are learning through trial and error, simulations, and huge amounts of real-world data. The progress represents a revolution in how machines interact with their surroundings.
It also means that Silicon Valley roboticists are dreaming big again. Here’s how we got here.
—James O’Donnell
This story is from the latest issue of our print magazine, which is all about nature. Subscribe now to read it in full.
The must-reads
I’ve combed the internet to find you today’s most fun/important/scary/fascinating stories about technology.
1 ICE plans to develop its own smart glasses
The “ICE Glasses” would identify people in real time. (404 Media)
+ ICE already uses an app with facial recognition to track citizens. (NYT $)
+ A new lawsuit wants to stop ICE using DNA to track critics. (Ars Technica)
2 AI is distorting key economic signals
It makes growth look better and the job market look worse. (WSJ $)
+ Welcome to the economic singularity. (MIT Technology Review)
3 A cyberattack paralyzed thousands of schools
And stole 275 million people’s data from edtech platform Canvas. (NYT $)
+ The digital learning software is used across the US. (CNN)
+ It’s the worst case scenario from an attack on one education platform. (Wired $)
4 The US suspects Nvidia chips were smuggled to Alibaba via Thailand
Super Micro servers containing Nvidia chips were allegedly smuggled. (Bloomberg $)
+ Through a firm linked to Thailand’s national AI initiative. (Reuters $)
5 China’s affordable AI models are increasingly worrying Silicon Valley
They’re often cheaper and more adaptable than US rivals. (Bloomberg $)
+ China is betting big on open source. (MIT Technology Review)
6 Scientists developed a new energy storage system inspired by sunburn
It stores solar energy by mimicking molecular changes in damaged DNA. (BBC)
+ Solar and wind with battery storage are becoming cost-competitive. (Reuters $)
+ Here are three other breakthrough climate technologies. (MIT Technology Review)
7 Russia’s internet crackdown is hobbling small businesses
App restrictions and internet outages are causing headaches. (Reuters $)
8 Younger researchers are more likely to produce “disruptive” science
A new study found more experience led to fewer breakthroughs. (Nature)
9 Why Richard Dawkins was mistaken to believe Claude has feelings
But his line of inquiry wasn’t altogether foolish. (The Atlantic $)
+ Why it’ll be hard to tell if AI ever becomes conscious. (MIT Technology Review)
10 The Golden Globes have new AI rules (and they’re looser than the Oscars’)
AI is permitted as an enhancement, but not as a replacement. (Gizmodo)
+ Last week, the Oscars banned AI actors and writing. (NPR)
Quote of the day
—Evolutionary biologist Richard Dawkins reflects on his interactions with advanced AI systems in an essay published in Unherd.
One More Thing
In a 10-month span in 2020 and 2021, southwest Louisiana saw five climate-related disasters, including two destructive hurricanes and flash floods. But there could be a better way to protect the area: elevation.
The $6.8 billion Southwest Coastal Louisiana Project is betting that raising buildings while restoring coastal boundary lands that have long acted as natural barriers can preserve this slice of coastline.
Here’s how officials hope to protect vulnerable communities by lifting homes out of the floodplain.
—Xander Peters
We can still have nice things
A place for comfort, fun, and distraction to brighten up your day. (Got any ideas? Drop me a line.)
+ Soaking in a hot tub might offer even more health benefits than a sauna.
+ A court has officially protected America’s largest rainforest from future logging.
+ Experience the majesty of the world’s largest owl collection through these intimate, high-detail portraits.
+ A dad has turned his toddler’s random stories into high-production pop songs that are surprisingly catchy.
Technology is changing the way we make babies. The pioneering work of the scientists who invented IVF led to the birth of the first “test tube baby” in 1978. We’ve come a long, long way since then.
This week, I’ve been working on a piece about the cutting edge of IVF technologies and what’s coming next. Think AI and robots and, potentially, gene-edited embryos.
My reporting has also made me think about just how much progress has been made in the last five decades. Clinicians have improved hormonal treatments. Embryologists have devised ways to culture embryos in the lab for longer. IVF clinics today offer multiple genetic tests for embryos.
In recent years, we’ve had reports of babies born with DNA from three people, babies born following “IVF on wheels,” babies born from decades-old embryos, and even babies “conceived” with the aid of a sperm-injecting robot.
The technology has also had a huge social impact. It has allowed for changes in the structure of families and provided more reproductive choices for would-be parents. So this week, let’s consider the technologies that have transformed babymaking.
Alan Penzias, a reproductive endocrinologist at Boston IVF, has been working in IVF since the early 1990s. In those days, his lab at Yale would collect a person’s eggs, fertilize them, and culture any resulting embryos for two days, until the embryos had two or four cells.
The embryos couldn’t survive any longer outside a body, so they’d be transferred to the uterus at that point. All of them. Even if there were, say, five embryos in total. Typical healthy patients could expect a live birth rate of 12% to 15%, he says.
Then Penzias heard that other teams were managing to culture embryos for three days. “We thought, No, that’s not possible,” he recalls. He learned that scientists had achieved this by tinkering with the culture medium—the nutrient-rich fluid the embryos are grown in.
Those three-day embryos, which had around six to 10 cells, seemed to have a better chance of resulting in a live birth. The teams culturing embryos for longer saw their success rates climb to 25% among similar patient groups, says Penzias. Again, he couldn’t believe it. “We thought they were making it up,” he says.
In the years since, teams have made more improvements to culture medium. Today, most IVF embryos are cultured for five or six days—a point at which they have 80 to 100 cells. The culturing process can act a little like a stress test—the embryos that make it to day six are generally more likely to go all the way and develop into a healthy baby.
Over the same period, advances in other technologies have opened up the options for what we can do with those embryos. Scientists learned they were able to freeze embryos and use them at a later date. A little over a decade ago, clinics shifted to a “vitrification” approach that rapidly cools the embryos to a glassy state. Vitrified embryos are more likely to survive freezing and thawing, so this approach quickly caught on.
As a result, doctors no longer needed to transfer multiple embryos at once. This made it less likely that patients would have twins or triplets, which can increase the risk of pregnancy complications.
Vitrification has also made IVF safer in other ways, including by affording patients a bit of time between fertility treatments. The hormonal treatments used in the first phase of IVF are designed to increase the production of mature eggs that can be collected. These treatments carry a small risk of a condition called ovarian hyperstimulation syndrome (OHSS), which in rare cases can be life-threatening. The ability to freeze all your embryos and use them at a later date is thought to give the body a chance to recover from hormonal treatment and reduces the risk of OHSS.
And because clinics are now able to culture embryos for up to a week, they can take a few of the 100 or so cells and send them for genetic testing before freezing the embryos. People undergoing IVF can get genetic readouts of all the embryos before deciding which to implant. (It is worth noting, however, that these testing technologies are not perfect.)
“Those are really radical changes, and we take them for granted,” says Penzias.
These technologies have also changed the function of IVF. What was once a treatment for infertility is now used to preserve fertility. People who want to delay parenthood can opt to freeze their eggs or embryos and use them later. They might opt to transfer one embryo in a year’s time and a second several years later. “We’ve been able to empower women to be able to have much more reproductive choice and get more reproductive mileage from a single IVF cycle,” says Penzias.
People who are about to undergo cancer treatments that might damage the testes or ovaries can opt to store their eggs or sperm ahead of time, too. Scientists have even been able to preserve pieces of ovarian and testicular tissue and reimplant them later, enabling recipients to have healthy babies.
Today, more people than ever have access to safe IVF options that offer multiple paths to parenthood. Those options look set to expand. But if you want to find out more about the AI and IVF robots, you’ll have to read this week’s story, here!
This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.
Macrophages are often described as the immune system’s first responders, but new work suggests they are also remarkably attuned to the physical state of their environment. A study published in the Journal of Cell Biology titled “Disruption of macrophage cell volume drives inflammatory responses and type I interferon signaling” reveals that shifts in cell volume act as a previously underappreciated danger signal—one that can rewire macrophage gene expression, heighten antiviral defenses, and intensify inflammatory responses.
The research, led by Jack Green, PhD, and colleagues at the University of Manchester, centers on the Volume‑Regulated Anion Channel (VRAC), a protein complex that helps cells maintain osmotic balance. When VRAC is missing, macrophages lose the ability to correct swelling under hypo‑osmotic stress. “Cell volume disruption induced type I interferon signaling through a DNA- and TBK1-dependent mechanism, but independent of cGAS and 2′3′-cGAMP transport,” the authors wrote. That loss of control, the team found, is far more consequential than a simple biophysical hiccup. It fundamentally alters how macrophages interpret threats.
Green noted that although earlier studies hinted at a connection between cell volume and inflammatory signaling, the underlying biology remained murky. “Despite the reported indications that cell volume and VRAC are involved in inflammatory signaling, the basic biological mechanisms of how the regulation of cell volume shapes inflammation were unknown,” he said. To probe that gap, the team examined VRAC‑deficient macrophages exposed to mild osmotic stress.
The swelling triggered broad reprogramming of gene expression, including the induction of antiviral and proinflammatory pathways. Many of the most strongly upregulated genes belonged to type I interferon signaling cascades or nucleic acid–sensing systems. First author James Cook frames the finding succinctly: “Together, these findings suggest that cell volume acts as an additional layer of danger sensing in macrophages that shapes and tunes the nature of immune responses to pathogens.”
That prediction held up in functional assays. When challenged with Influenza A virus, VRAC‑deficient macrophages mounted a more potent antiviral response than their wild‑type counterparts. The heightened sensitivity extended beyond viral infection. In mouse models of systemic hyperinflammation, animals lacking VRAC showed elevated levels of a key inflammatory mediator, indicating that dysregulated cell volume can exacerbate cytokine‑driven pathology in vivo.
Rather than responding solely to biochemical cues, these cells appear to fold physical perturbations—such as osmotic imbalance—into their danger‑sensing logic. Green argued that this perspective may help explain why inflammatory diseases can escalate unpredictably when tissue conditions shift. “Understanding disruptions in the tissue microenvironment leading to alterations in cell volume is therefore an important consideration in our understanding of inflammation and disease pathogenesis,” he concluded, adding that “future studies will reveal the potential for regulating VRAC‑dependent cell volume changes in macrophages in disease.”
The post Macrophages Use Cell Volume Changes to Sense Danger and Amplify Inflammation appeared first on GEN – Genetic Engineering and Biotechnology News.
Vyriad reports that it will showcase its latest CAR T delivery technology platform, G-Link, through a schedule of presentations, technical sessions, and exhibition activities at ASGCT. The modular plug-and-play protein adapter developed in collaboration with Menachem Rubenstein, PhD, of the Weizmann Institute allows drug developers to cap and retarget existing lentiviral vectors for in vivo delivery, according to the company.
By leveraging G-Link, wild-type lentiviral vectors can be reprogrammed for in vivo applications without the need for intensive vector re-engineering, effectively shortening development timelines for next-generation CAR T and other cell therapies, notes a company spokesperson, who adds that G-Link can also be used to simplify ex vivo CAR T manufacturing and significantly improve T cell transduction efficiency without redesigning vectors.
“I believe that G-Link can address some of the most persistent challenges in in vivo delivery and we are excited to unveil it at ASGCT this year,” says Stephen Russell, PhD, CEO of Vyriad. “Our participation this year underscores our clear mission: to replace complex, weeks-long manufacturing cycles with precise, off-the-shelf immunotherapies. With G-Link, we aim to foster collaborations that will define the next generation of in vivo cell therapies.”
Vyriad’s VV169 in vivo CAR T program will progress into clinical development later this year, while the G-Link platform will advance towards clinical translation later in the future, continues Russell.
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Scientists at La Jolla Institute for Immunology (LJI) say they are the first in the world to characterize human monoclonal antibodies (mAbs) capable of neutralizing measles virus (MeV). The antibodies, derived from the memory B immune cells of an individual who had previously received the MMR vaccine years previously, bind to key hemaggglutinin (H) and fusion (F) surface virus proteins, preventing viral entry into host cells.
The researchers, headed by Erica Ollmann Saphire, PhD, LJI professor, president, and CEO, say the new panel of human antibodies may form the basis for future medical therapies against measles infection. In their newly reported study the team showed that an infusion of the antibodies resulted in 500-fold lower viral load in a rodent model of measles infection.
“These antibodies work as prophylaxis—to protect from initial infection—and they work after viral exposure as a treatment to fight measles infection, said Saphire. “It may be possible to give someone an infusion of these antibodies and deliver the immune response they wish they had.”
In their study (“Human neutralizing antibodies targeting the measles virus hemagglutinin and fusion surface proteins”) reported in Cell Host & Microbe, the team concluded “Characterization of these fully human mAbs provides avenues for prophylactic or therapeutic intervention against re-emerging MeV.”
Measles virus is “… a highly transmissible paramyxovirus, can cause severe complications and death, particularly in infants and young children,” the authors wrote. “A live-attenuated vaccine derived from a genotype A MeV strain provides vaccinees with lifelong immunity and protective antibodies against all 24 MeV genotypes in circulation.”
However, in recent years, decreased vaccination rates have led to deadly measles outbreaks across the U.S. and around the world. This sharp rise in measles cases is especially dangerous for the millions of people who cannot receive a measles vaccine. While the measles vaccine is incredibly safe and effective, it does contain a live, weakened virus. This means that people who have compromised immune systems, such as those who are pregnant or receiving chemotherapy, including children, cannot receive the vaccine. The very young are also at risk. Infants must wait until they are 12 months old to be vaccinated, and most children in the U.S. aren’t fully vaccinated against measles until they are six years of age.
“There are a growing number of people that can’t be vaccinated or haven’t been fully vaccinated,” said Saphire. “The very same people who can’t be vaccinated or can’t be vaccinated yet, are the same people for whom a measles virus infection would be the most severe—or be lethal.”
Until recently, enough people were vaccinated against measles virus that the risk of exposure for this unvaccinated group was very low. Unfortunately, that community protection—herd immunity, is no longer. LJI scientists are on a mission to find treatment options for the most vulnerable.
There are currently no measles-specific therapies to help patients. The new study shows that monoclonal antibody therapies may may be a feasible option. Monoclonal antibody treatments contain many copies of a neutralizing antibody, and are widely used for a variety of infectious diseases. Even infants receive monoclonal antibody therapies each year to prevent respiratory syncytial virus (RSV).
To design a monoclonal antibody treatment for measles, researchers need a clear picture of how human antibodies fight the virus. However, as they noted, “Despite the global presence of MeV and widespread use of the vaccine, few studies have mapped the human antibody response. We do not yet know how human antibodies, from either measles vaccination or natural infection, recognize and protect against the virus.”
Saphire and her colleagues began by harnessing an imaging technique, cryo-electron microscopy (cryo-EM), to capture the first-ever glimpses of how antibodies bind to the measles virus. They started by examining mouse antibodies, and published that work in a recent paper. That initial study showed where measles virus is vulnerable to antibody attack. The mouse antibodies, the researchers showed, latched onto the virus fusion protein, to block viral entry into a cell.
To find out whether human antibodies could do the same thing, the researchers analyzed blood from a clinical research volunteer. “We evaluated 15 MMR-vaccinated donors for their polyclonal MeV responses to identify individuals with vaccine-induced, protective, circulating antibodies,” they explained. The 56-year-old female volunteer they selected had been vaccinated against measles many years before, and already had antibodies ready to fight measles virus. This individual “… demonstrated the highest polyclonal response and the most H- and F-reactive memory B cells.”
From the one blood sample, the LJI scientists isolated antibodies that bind to the measles virus fusion protein, along with other antibodies that bind to the virus hemagglutinin protein. They then captured 3D images of these antibodies bound together with the measles virus. “We found that these antibodies are exceptionally potent,” said study first author, LJI Instructor Dawid Zyla, PhD. “Two orders of magnitude better than comparable molecules reported at conferences.”
Measles virus is a shape-shifting virus. When it meets a human cell, it unfolds to reveal viral machinery that fuses with the host cell membrane. The new study shows that antibodies targeting the fusion protein work by locking the protein in place, leaving the virus unable to shape shift and infect a host cell. The next step was to test these antibodies in a preclinical animal model. Study collaborators at The Ohio State University carried out key experiments in cotton rats. They found that all four lead antibodies reduced viral load when given either before measles exposure or within 24 to 48 hours after measles virus infection. One antibody, designated 3A12, which binds to a site on the F protein, rendered the circulating virus actually undetectable.
While more work needs to be done, the researchers see these antibodies as promising tools in the fight against measles. Their new images of the antibody structures provide the materials needed to make the world’s first before- or after exposure treatment for measles virus. “Now we know what we’re aiming for, and we have the antibodies we need,” said Saphire.
In their paper the authors stated, “The protective mAbs identified here target four distinct, non-competing epitopes, and may be combined as cocktail therapies to enhance treatment potency, maintain durable protection, and reduce the risk of viral escape.… these human mAbs themselves, which recognize conserved sites and inhibit measles by complementary mechanisms, represent a basis to develop a treatment that is urgently needed as measles virus infections surge globally.”
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