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.
A research team led by scientists at the Princess Máxima Center for Pediatric Oncology, the University of Michigan Medical School, EMBL European Bioinformatics Institute, and the Institute for Systems Biology, has uncovered more than 1,700 new proteins that could have implications for human diseases, including cancer.
Mostly very small, these proteins have been discovered in what’s known as the “dark proteome,” which covers gene products from previously overlooked sections of DNA. These proteins have unusual properties, motivating scientists to coin a new concept, peptideins, to help understand their potentially unique biology. Research co-lead Sebastiaan van Heesch, PhD, a group leader at the Princess Máxima Center, commented, “We know that the current overview of recognized proteins doesn’t capture the full picture. With this study, we show that thousands of overlooked genetic sequences contribute to the dark proteome by producing a new class of protein-like molecules, microproteins, that had been missed before now. But for most of them, we don’t yet know what they do.”
Research co-lead and co-corresponding author Robert Moritz, PhD, professor and head of proteomics at the Institute for Systems Biology, further noted, “Biology has long relied on a relatively small cast of well-characterized proteins to explain the regulatory logic of the cell, but peptideins suggest that beneath that familiar layer lies an entire untapped layer of molecular actors whose functional roles in gene regulation, signaling, and cytopersistence, many we are only beginning to imagine. Given their smaller size and the diversity of cellular contexts in which they appear, I believe peptideins may prove to be among the most versatile and consequential regulatory molecules we have yet encountered in human biology. This is not the end of a search—it is the opening of a vast and fertile new territory for the entire scientific community to explore and exploit, and I look forward to seeing what the broader scientific community uncovers as these molecules, and many more that are yet to be confirmed, are brought into the light.”
Research co-lead John Prensner, MD, pediatric neurooncologist at the University of Michigan Medical School, together with Van Heesch and Moritz, are co-senior and co-corresponding authors of the researchers’ published paper in Nature titled “Expanding the human proteome with microproteins and peptideins.” The team is sharing its discoveries with scientists worldwide in an open-source format to stimulate further research.
Van Heesch added, “With growing interest in industry and academia, peptideins are at the center of multiple drug development initiatives. Similarly, we see them increasingly turning up as important players in diseases, including childhood cancers. We hope to inspire a new wave of research into peptideins and to unlock new insights and drug targets across human biology, particularly for the development of cellular immunotherapies and cancer vaccines.”
The study is the work of the TransCODE Consortium, an international collaboration of more than 60 researchers at over 30 institutions worldwide, co-led by the Princess Máxima Center for Pediatric Oncology in the Netherlands, the University of Michigan Medical School, the EMBL European Bioinformatics Institute in Hinxton, and the Institute for Systems Biology in Seattle.
Genes in DNA provide the recipe for cells to produce peptides. Historically, peptides have been called proteins if they are long enough and have existing evidence for a biological role, such as the appearance of the same protein across species in evolution. “Protein-coding genes are the bedrock of biomedical investigations, including the overwhelming majority of drug development programs,” the authors wrote. A large, curated international database of proteins contains some 19,500 entities.
But increasingly, scientists believe the traditional definition of a protein needs to be broadened. “Whether the human genome encodes substantially more than the approximately 19,500 canonical protein-coding genes has sparked a spirited debate in recent years,” the scientist continued. “Therefore, any wholesale addition of protein-coding genes creates ripple effects across human bioscience.”
Through their newly reported study the team looked at more than 7,200 previously understudied sections of the DNA called non-canonical open reading frames (ncORFs). They found that some 25% of these sections—more than 1,700—generated detectable protein-like molecules. These proteins, smaller than traditional proteins, are referred to as “microproteins.”
Generating their results involved looking at 3.7 billion individual bits of raw data that may support known and previously unknown proteins—drawing upon 95,520 experiments. “We show that about 25% of a set of 7,264 ncORFs gives rise to detectable peptides in a large-scale analysis of 95,520 proteomics experiments,” they wrote. The process took around 20,000 hours for computers to complete, working non-stop. They found 1,785 microproteins, a number that at first glance would increase the protein databases by nearly 10%.
Predicted binding between a non-canonical open reading frame (blue) and traditional protein (yellow). [Leron Kok/Princess Máxima Center for Pediatric Oncology]
Moritz further explained, “By deploying our battle-hardened Trans Proteomic Pipeline across nearly 100,000 mass spectrometry experiments encompassing 3.7 billion spectra—derived from the world’s collective publicly available mass spectrometry data, with the results housed within PeptideAtlas at ISB for the scientific community to view and share—we were able to confirm, with high confidence, the existence of more than 1,700 of these newly identified peptideins that would otherwise have largely remained invisible to science.”
But most of these 1,785 microproteins didn’t resemble the other 19,500 traditional proteins. For example, they were very small: 65% were fewer than 50 amino acids in length, compared to less than 1% of the 19,500 previously catalogued. Looking more closely at the microproteins the investigators saw that only a few—perhaps a dozen—resembled the traditional proteins. The team then spent more than a year trying to make sense out of the remaining bulk.
Working with protein experts from across the globe in the TransCODE consortium, the scientists coined a new biological concept, which they coined peptidein. For decades, the research community has had a binary view of the relationship between human DNA and human proteins. A given piece of DNA either does or does not produce a protein. In their new study, the scientists propose a third choice, which is that DNA could make a protein, a peptidein, or neither.
The team defined a peptidein as existing in cells as a protein-like molecule, meaning that it is made of amino acids, as are proteins. But the role of a peptidein is ambiguous. Perhaps it has a function in normal human biology, or perhaps not; this is the key distinction with traditional proteins, where all are believed to have a function in normal human biology even if the details of that function are not fully known yet. “To advance these ncORFs in biological inquiry, we invoke the emerging umbrella term of peptidein, which we define as an ORF with experimentally confirmed RNA translation and protein synthesis, but for which the data are currently insufficient to claim conventional protein-coding gene status,” the investigators stated in their report.
Importantly, this definition of peptidein leaves the door open for it to become a ‘protein’ in the future—that is, if scientists gather more evidence on it. To start exploring this idea, the team searched for peptideins without which cells cannot survive. These so-called pan-essential peptideins can be important candidate drug targets in cancer and other diseases.
Using large-scale CRISPR gene editing, the scientists found six peptideins that looked promising. For example, one of these was a peptidein produced from OLMALINC, a genetic sequence previously thought not to produce proteins. When the researchers switched this gene off, 85% of more than 485 cancer cell lines showed impaired survival. The researchers confirmed that this effect comes from the peptidein itself, not the RNA molecule it sits on, and found that it plays a role in cell division and DNA damage response. “Our work here highlights c10riboseqorf92 (in the OLMALINC transcript),” they commented. “… while we do not yet have sufficient evidence that this ncORF encodes a bona fide protein, its CRISPR-based phenotypes in the context of cancer cells are intriguing.”
Many of the newly detected peptideins are presented on cell surfaces for recognition by the immune system, making them potential targets for cancer immunotherapy. A number of such molecules presented to the immune system are already under development as drug targets, and there is growing interest from both academia and industry in exploiting this new class of cancer antigens. Peptideins could also shed light on genetic diseases that conventional gene analysis has been unable to explain, simply because genetic diagnostics were unaware that these molecules were encoded by the human genome.
Members of the consortium had previously uncovered an essential role for a microprotein, ASNSD1-uORF, in children with a high-risk form of the brain cancer, medulloblastoma. Scientists at the Princess Máxima Center are now carrying out further research to determine its role in additional pediatric cancers with the activated MYC oncogene, such as neuroblastoma.
van Heesch commented, “It felt really special to discuss and decide what to do with this new class of molecules, as we had gathered enough early evidence to suspect that they might be widespread across cell types and tissues. By classifying these molecules of unknown functionality as peptideins, we’ve given them a formal place in reference databases so the wider community can study them.”
In their paper the researchers concluded, “The extent of the undiscovered proteome is one of the central questions in human biomedicine. This work reflects the multi-consortium collaboration between the TransCODE Consortium, the HUPO-HPP/PeptideAtlas project, the HIPP immunopeptidomics project and the GENCODE gene annotation group to coalesce a generalizable approach towards understanding which ncORFs can be understood as encoding proteins … Through our efforts, we bring microproteins and alternative protein molecules into reference gene annotation by defining them as either a protein-coding gene or a peptidein, a new concept referring to confirmed protein molecules of indeterminate consequence.”
Prensner added, “We’re just beginning to see what this ‘dark proteome’ has to offer. It’s like the trailer to a movie. We see the outline of a game-changing view of human biology. We’re incredibly excited that the coming years will open new doors to help solve and treat human diseases such as cancer.”
Moritz further stated, “Our collaborative work represents a culmination of decades of investment from federal funding agencies in building the computational and data infrastructure needed to interrogate the proteome at truly unprecedented scale at the Institute for Systems Biology … What excites me most is not simply that these molecules exist, but what their existence implies.”
The researchers are making we make all ncORFs, peptides and spectra publicly available through PeptideAtlas.
ObjectiveThis study aims to investigate the correlation between trace element concentrations, 25-hydroxyvitamin D [25(OH)D] levels, and the severity of tic disorders (TD) in children from the Hubei region. Additionally, it seeks to explore the interrelationships among these monitored indicators to provide a reference for the clinical diagnosis and treatment of pediatric TD.MethodsA retrospective review was conducted on the medical records of 237 children diagnosed with TD (TD group) and 137 healthy controls, admitted to the Department of Neurology at Hubei Maternal and Child Health Care Hospital. The TD group was further divided into mild and moderate-to-severe subgroups based on the Yale Global Tic Severity Scale scores. General clinical data were collected, and serum trace element levels were measured using inductively coupled plasma mass spectrometry (ICP-MS), while serum 25(OH)D levels were quantified via liquid chromatography–tandem mass spectrometry (LC–MS/MS). Group comparisons, Spearman correlation analysis, and univariate/multivariate logistic regression analyses were performed.ResultsThe findings indicated that serum 25(OH)D levels were significantly lower in children with TD compared to controls (p < 0.001). Logistic regression analysis demonstrated that 25(OH)D was an independent protective factor against tic disorders.(p < 0.001). Compared to the control group, children with TD exhibited significantly lower levels of calcium and copper (p < 0.001), along with higher levels of iron and cadmium (p < 0.01). These differences were more pronounced in the subgroup of children older than 6 years. An age-stratified subgroup analysis revealed no significant differences in any other indicators except for cadmium between the TD and control groups among children aged 6 years or younger (p > 0.05). Spearman correlation analysis demonstrated that within the TD group, 25(OH)D levels had the most significant correlations with calcium and copper (p < 0.001). No statistically significant differences were observed in the levels of the 10 trace elements or 25(OH)D between the mild and moderate-to-severe TD subgroups (p > 0.05).ConclusionChildren with Tic Disorders in Hubei Province demonstrate a distinctive alteration in their micronutrient profile, primarily characterized by a deficiency in 25(OH)D, alongside reduced levels of calcium and copper, and elevated levels of iron and cadmium. This association is particularly pronounced in male children over the age of six. While 25(OH)D deficiency is identified as an independent risk factor for TD, its concentration does not significantly correlate with the severity of the disorder.
This Comment discusses depth, robustness and bias in plasma proteomics, concluding that increasing the depth of coverage does not necessarily translate to quantitative robustness.
For individuals with APOL1 high-risk genotypes, which are enriched in individuals of African ancestry, a nine-protein proteomic risk score enables early prediction of kidney disease progression and may, thereby, enable early intervention.
This Resource presents a large-scale analysis of nearly 3,000 circulating plasma proteins across the menstrual cycle in over 2,700 women from the UK Biobank, revealing distinct proteomic patterns across menstrual phases. This work sheds light on female reproductive biology and gynecological disorders, and provides a proteomic signature for accurate prediction of the menstrual cycle phase.
A limiting feature of many neurological therapies is the ability of molecules to cross the blood-brain barrier (BBB) from the circulatory system. Since the BBB prevents simple diffusion of materials across the divide, identifying the proteins responsible for transport is necessary for effective design of BBB-crossing therapies.
“So basically, everything in the circulating blood, if they want to have an exchange with the organ, they need to pass through this interface,” says senior author Jiefu Li, PhD, Janelia Research Campus Group Leader at the Howard Hughes Medical Institute.
Identification of the structures within blood vessels involved with the processes of molecular movement across the BBB has been somewhat elusive. However, Li and his team have developed a technique that not only identifies proteins within the luminal surface—the inner lining—of the vasculature, but also works in vivo, allowing them to track how these features change across the aging brain.
“Understanding how the blood-brain barrier works, particularly figuring out the molecular targets that you can play with to open and close the barrier, will provide new possibilities for drug delivery,” Li says.
Using mice, the team developed a proteomic profiling method that can be used not only in brain vasculature, but throughout the body. “Briefly, a lectin-conjugated peroxidase is perfused and anchored to the luminal surface of blood vessels to catalyze the biotinylation of adjacent proteins, thereby enabling subsequent protein enrichment and mass spectrometry analysis,” wrote the authors.
They tested the method in the brain, kidney and intestine, in both mice and northern tree shrew, showing functionality and applicability across organs and species.
“This will allow us to say: we know that the vasculature system is doing different things in different organs and it relies on this luminal surface, but how does that happen? What are the molecular players there?” Li says.
Using quantitative proteomics of the luminal surface—from early development through adulthood and aging—they found that over time there was a decrease in angiogenic and transport proteins. They also found an increase in proteins that increased stiffness in the vasculature.
In addition to developing this in vivo technique, the team identified two proteins that are temporally distinct in their expression while both playing a role in modulating BBB permeability. Knockouts of nitric oxide synthase Nos3 and arginine transporter Slc7a1 resulted in BBB leakage in neonates, but not adults, while genetic screens identified hyaluronidase HYAL2 as being required for maintaining BBB integrity throughout the lifespan of mice.
“What we know now is that we have two new pathways, potentially, to open the blood-brain barrier and to inform some therapeutic developments,” says Li.
Utilization of this proteomic based method in vivo both opens up new avenues of functional research across the cardiovascular system, and also provides data and a methodology for novel therapeutic targets for crossing the BBB.
“This method solves an important need but it’s also a very easy-to-use method, so everyone can use it,” Li says.
This week, Seer, a developer of proteomics technology, said that scientists involved in the PRECISE-SG100K initiative will use the company’s Proteograph® product suite to profile the plasma proteome of about 10,000 participants. The data from this workflow will be combined with information from the same participants that was generated using Thermo Fisher Scientific’s Olink® Reveal, a next-generation sequencing-based proteomics solution, and its Orbitrap Astralmass spectrometers.
PRECISE-SG100K is the second phase of a broader initiative in Singapore that aims to support various research studies that advance scientists’ understanding of health and diseases. Touted as a landmark population study of approximately 100,000 Singaporean residents, PRECISE-SG100K is designed to integrate genomic, proteomic, lifestyle, imaging, and other health data from a multi-ancestry Asian population. By combining data from Seer’s Proteograph platform alongside information from other technologies that are being used for the project, the scientists aim to develop what they believe will be one of the most comprehensive multiomic datasets available to date.
“PRECISE-SG100K is one of the most ambitious and carefully designed multiomic health initiatives in the world,” said Omid Farokhzad, MD, PhD, chair and CEO of Seer. And that fits with Seer’s vision for Proteograph, which was that “deep, unbiased proteomics becomes the mainstay for population-scale multiomic studies.”
Seer already has an existing relationship with Thermo Fisher dating back several years. In 2024, the companies announced a co-marketing and sales agreement that allowed Thermo to jointly promote Proteograph alongside Orbitrap Astral mass spectrometers to provide customers of the Orbitral Astral with an integrated solution for unbiased proteomic analysis. The combined solutions have since been used in a number of large population studies providing high-throughput, deep proteome coverage.
“A key goal of PRECISE-SG100K is to create a deeply characterized, multi-ancestry resource that can reveal how genetics, environment, and lifestyle shape disease risk and treatment response,” said John Chambers, PhD, chief scientific officer of PRECISE and lead principal investigator of the PRECISE-SG100K study. “By adding deep, unbiased plasma proteomics enabled by Seer and Thermo Fisher, we can more directly link genomic variation to protein networks and health outcomes, uncovering insights critical to ensuring precision medicine reflects the diversity of Asian populations.”
Ultimately, the data generated from population projects like this are expected to support biomarker discovery in key disease areas including cardiometabolic, ophthalmic, and neurologic disorders. They could also inform the development of predictive models for assessing disease risk and response as well as efforts to validate and prioritize biomarkers identified through affinity-based platforms.
Plant molecular farming (PMF) may seem like a bold option for companies accustomed to mammalian or microbial systems, but recent advances have transformed plant-based bioproduction into serious, scalable biomanufacturing platforms able to produce even complex biologics cost-effectively.
“A major advantage is sustainability,” Marco P.C. Marques, PhD, associate professor, University College London (UCL), tells GEN. This comes at a time when “…regulators and global initiatives are putting real pressure on industry to reduce environmental footprint(s). Because plants grow using low energy inputs rather than stainless steel reactors or energy-intensive systems, they can bring down operating costs, reduce carbon emissions, and provide more flexible manufacturing options.”
Additional benefits include PMF systems’ ability to support eukaryotic protein-folding and post-translational modification pathways, their lack of human pathogens, minimal biosafety risks, and compatibility with distributed manufacturing.
PMF reached its current state because sensors, host plant engineering, AI-enabled models, and related technologies have become more mature, reliable, and predictable in the past few years. Consequently, “PMF platforms can deliver consistent, good manufacturing practice (GMP)-compatible performance while needing far less infrastructure, [which] allows much faster setup than conventional approaches,” Marques says.
Robust, economic, responsible
In a recent paper, he and first author Teresa Iucci, PhD, a bioprocessing scientist at Sapienza University of Rome and UCL, cite 13 companies that are using or have used plants to produce a variety of proteins, including antibodies, enzymes, and peptides, for vaccines and other biologics. Many are at clinical or commercial scale.
Those examples show “that controlled cultivation, advanced transient-expression systems, and more refined downstream workflows can overcome many of the technical and regulatory hurdles historically associated with plant-based biomanufacturing.” In particular, they note substantial improvements in host plant engineering. Now, they point out, Nicotina plants can produce mAbs and Fc-fusion proteins that closely match those derived from CHO cells.
However, “Realizing the full value of these biological innovations will depend on aligning PMF with contemporary digital manufacturing principles,” Iucci and Marques stress.
“There is a lot of scope for continued innovation…particularly on the molecular biology side, where further gains in expression, stability, and product quality are very achievable,” Marques elaborates. “Downstream processing could also be better tailored to plant-based hosts,” to lower costs further.
The benefits of PMF are well-recognized, but biomanufacturers also need clear, streamlined regulatory pathways and the internal determination that PMF is worth sustained investment.
For biomanufacturers, “A good starting point is simply to treat PMF as a genuine production platform rather than an interesting alternative,” he says. To be able to compare PMF products with those derived from traditional mammalian or microbial cultures, he calls for the industry to standardize unit operations and generate regulatory-grade datasets, and then to run comparability studies and pilot-scale campaigns.
Running such campaigns is becoming increasingly practical with the conjunction of sensors and data-driven processors. In vertical farming facilities, for example, every parameter critical for plant growth is tightly monitored and controlled using digital sensors to enable precise, real-time environmental adjustments.
Ultimately, this allows producers to select the optimal timing of such events as infiltration and harvest at levels not possible in conventional greenhouses. “The long-term objective is a semi-continuous, digitally regulated PMF production line that links infiltration, extraction, and purification into a coherent, self-correcting workflow,” Iucci and Marques write.
Transitioning from mammalian or microbial systems to PMF, “is easier said than done…especially when companies already have well-established mammalian or microbial platforms with validated processes and established supply chains,” Marques acknowledges. “In many respects, it would be simpler to design a PMF-based approach from scratch than to retrofit it into an existing operation…but with the right incentives (such as additional revenue streams from side processes), application cases, and evidence, we may well see more companies prepared to make that shift.”
BackgroundEsketamine has a significant and rapid antidepressant effect. Although studies have shown that Neuregulin 1 (NRG1) and it’s signaling pathway are associated with depression, the possible regulatory relationship of esketamine on the NRG1-ErbB4 pathway is not yet clear.MethodsTo induce depressive-like behavior in mice, a Chronic Social Defeat Stress (CSDS) model was established. Behavioral indicators were then employed to assess depression in these mice, categorized into control, susceptible, and resilient groups. Following intraperitoneal injection of a subanesthetic dose of esketamine, behavioral tests were conducted at 30 minutes and 24 hours post-injection to observe any improvements in depressive-like behavior. Additionally, changes in immunofluorescence and protein expression levels of NRG1-ErbB4 and GAD67 in the prefrontal cortex were evaluated.ResultsCompared with the control group, the CSDS susceptible group mice showed decreases in social interaction ratio in the contact area, sucrose preference ratio, NRG1 immunofluorescence protein expression in the prefrontal cortex and NRG1 expression in tissue homogenate; showed significant increases in immobility time; the expression of NRG1 decreased;no significant change in GAD67 and ErbB4 expression level. in After 30 minutes of intraperitoneal injection of esketamine, the expression of NRG1 in the prefrontal cortex of susceptible mice increased significantly. no significant change in GAD67 and ErbB4 expression level. After 30 minutes and 24 hours of intraperitoneal injection of esketamine, the social interaction ratio of susceptible group improved compared to the control group, and the duration of forced swimming immobility was significantly shortened.ConclusionThe subanesthetic dose of esketamine may regulate the NRG1-ErbB4 signaling pathway and improve depressive like behavior in mice.
) 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.![Predicted binding between a non-canonical open reading frame (blue) and traditional protein (yellow). [Leron Kok/Princess Máxima Center for pediatric oncology]](https://www.genengnews.com/wp-content/uploads/2026/05/Low-Res_Protein-structure-copyright-Leron-Kok-Princess-Maxima-Center-300x201.jpg)