<![CDATA[How AI can aid everyday psychiatry—TRD prediction, suicide risk, and smartphone phenotyping—plus why data quality and workflow still block adoption.]]>
Gorilla Adenovirus Brings Natural Edge to Cancer Therapy
When ReiThera’s scientists first turned to a gorilla-derived adenovirus, they were thinking about vaccines. What they found instead might reshape how the field thinks about virus-based therapy for cancer.
Angelo Raggioli, PhD, head of technology development at ReiThera, describes a platform built on a gorilla adenovirus that was discovered, not designed. He adds: “Several therapeutically relevant properties appear to be embedded in the native biology of the vector itself.” For example, the group C gorilla adenovirus showed low seroprevalence in humans, reduced liver sequestration after systemic delivery in mouse models, a natural tendency to go to the lungs, and intrinsic replication selectivity in human cancer cells, sparing non-cancerous cells.
That combination addresses some of the most persistent obstacles in virus-based therapy. Pre-existing immunity against common vectors can blunt therapeutic efficacy before treatment begins, while off-target organ uptake—particularly hepatic sequestration of adenoviral vectors—remains a fundamental challenge for intravenous administration. A gorilla-derived isolate sidesteps both problems: it is naturally distant from human adenoviruses (avoiding the impact of pre-existing immunity shaped by prior exposure), and serendipitously avoids liver sequestration.
The biodistribution profile is equally important. Reduced liver targeting after systemic delivery, plus an attraction to the lungs, positions the platform not only for oncology applications but potentially for pulmonary gene therapy.
Raggioli adds that adenoviral vectors offer cargo capacities of about 36 kilobases, which is a significant advantage over the roughly 4.5-kilobase ceiling of adeno-associated viruses. For diseases requiring delivery of large transgenes, that capacity difference could be clinically decisive.
In oncology settings, the vector has demonstrated selective replication in tumor cells while sparing normal tissue, which was a property the ReiThera team observed rather than engineered. “While much of the field is actively engineering vectors to retarget specific tissues, in this case, we started from the natural tropism of the virus and began exploring how to leverage those native biological properties therapeutically,” Raggioli explains.
The platform has also been armed with therapeutic payloads. As a proof of concept, the team encoded a single-chain anti-HER3 antibody directly into the viral genome, achieving selective expression in replication-permissive tumor cells. This positions the platform within a broader trend in oncolytic virology: viruses are increasingly expected to serve not merely as cytolytic agents but as localized delivery systems for antibodies, immune modulators, and other complex biologics.
That evolution reflects a shifting understanding of how oncolytic viruses actually work. Tumor cell lysis alone is no longer considered sufficient; the immunological consequences of that lysis—whether it triggers a productive antitumor immune response—are central to therapeutic activity. Engineering for that immunogenic conversion while preserving replication potency and tumor specificity represents one of the field’s most demanding design challenges.
“An additional strength of the platform is that, for vaccine and oncolytic applications, we can manage the entire process internally, from genome engineering to clinical-grade manufacturing,” Raggioli says.
What began as a search for a better vaccine backbone has yielded something potentially more versatile: a vector whose biology may be doing therapeutic work that other platforms have to build in from scratch.
The post Gorilla Adenovirus Brings Natural Edge to Cancer Therapy appeared first on GEN – Genetic Engineering and Biotechnology News.
Updated Amplification Tool Rapidly Detects Mycoplasma
Nucleic acid amplification techniques (NAAT) are recommended by pharmacopoeias in the United States, the EU, and Japan as an alternative to traditional culture and indicator cell methods used to detect Mycoplasma in biological products. Used for in-process controls and release testing, NAAT is an improvement over traditional methods that take up to 28 days, but attempts to balance broad species coverage and sensitivity favor one over the other.
Recently, Chinese researchers developed a NAAT that overcomes those challenges, according to a recent paper by scientists at the National Institute for Food and Drug Control, Yeasen Biotechnology, and Xi’an Jiaotong-Liverpool University.
Rather than surpassing existing technologies, “It optimizes the core pain points of mainstream multiplex NAATs,” encompassing their advantages and forming others, senior author Xiaoliang Sun, PhD, scientist, genomics division, Yeasen Biotechnology, tells GEN.
For example, for cell therapy products, Sun says this NAAT technique, “cuts mycoplasma tests from a 28-day culture to several hours, enabling same-day batch release and avoiding cell product expiry scrap.” It also “accelerates finished-product release for short shelf-life recombinant proteins and monoclonal antibodies.”
The three pairs of primer-probe sets in this assay cover 183 Mollicutes species by targeting Mycoplasma-specific conserved regions. “This fills the detection gap [experienced by] some rare strains…and makes it suitable for trace contamination screening in biopharmaceutical production,” Sun points out.
To objectively assess this method, they compared it to traditional 165 rRNA degenerate PCR, strain-specific NAATs, and mainstream multiplex NAATs cited in the literature.
The analysis shows the new assay offers “single-copy detection sensitivity (validated by 10 pharmacopoeia standard strains), no cross-reactivity (validated with 14 non-Mycoplasma genera and six engineered cell lines), short amplicons of 100 to 200 bp, amplification efficiency of 95–105%, and excellent repeatability,” Sun says. This ensures specificity and improves detection consistency. Consequently, the method “meets the strain detection requirement of Chinese and European pharmacopoeia for full-process regulatory scenarios.
“The detection process is compatible with existing qPCR platforms without requiring special equipment and can be directly applied to full-process scenarios, such as raw material screening, cell bank verification, and finished product release,” Sun continues, “achieving more comprehensive compliance.”
There are limitations, though. “Detection performance for unrecorded Mycoplasma strains from extreme environments or highly variable subspecies has not been verified… leaving a potential detection gap,” he cautions. Additionally, “The use of three pairs of primer-probe sets increases the reagent cost per sample.” Therefore, scientists may best use this method for initial screening, followed by digital PCR confirmation.
For biopharmaceutical manufacturers, Sun says this assay’s main advantages are “comprehensiveness, stability, and practicability.” Future work is envisioned to expand the assay’s applicability parameters and robustness.
The post Updated Amplification Tool Rapidly Detects Mycoplasma appeared first on GEN – Genetic Engineering and Biotechnology News.
Innovative Tech Testing in Response to GMP Revisions
Recent revisions to EU manufacturing guidelines are changing how drug makers test processing technologies, according to the author of a new study, who cites growing use of an approach known as PUPSIT as an example.
PUPSIT, or pre-use post-sterilization integrity testing, is used to verify the integrity of sterilizing-grade filters after they have been sterilized, but before they have been used in a biopharmaceutical manufacturing process.
The idea is to make sure the filter has not been compromised during handling or sterilization and is still capable of retaining microorganisms, according to lead author Martin Glanz, Dr. rer. nat., senior principal scientist at Cytiva.
“Operationally, this typically involves wetting the membrane, venting the system, and then carrying out an integrity test such as a bubble point or forward-flow test. These methods essentially measure gas flow through the wetted membrane and confirm whether the filter meets its defined specifications,” he tells GEN.
Conventional verification processes focus on testing filters after they have been used, which, Glanz says, means that faults can be missed.
“The main benefit of PUPSIT compared to older approaches, which often relied heavily on post-use testing, is that you detect any potential defects before product exposure.
“That’s quite important, because defects can sometimes be masked during filtration— for example, due to fouling or plugging—and might not show up afterward. PUPSIT helps close that gap and strengthens overall sterility assurance,” he says.
The biopharmaceutical industry’s use of PUPSIT has increased since 2022, when EU GMP Annex 1, which covers the manufacture of sterile drugs, was revised to include stricter environmental monitoring and quality control requirements.
Glanz adds, “Even though PUPSIT isn’t always an absolute requirement, it is generally expected unless there is a well-justified, risk-based rationale not to perform it. Through PIC/S, this expectation is spreading beyond Europe as well.”
Adoption challenges
Switching from post-use verification strategies has significant potential benefits. However, implementing the approach can be challenging because, compared with traditional approaches, PUPSIT requires some additional steps, Glanz says.
“Companies often run into issues such as increased process complexity: you’re adding steps like wetting, venting, and testing that need to be controlled carefully.
“Additional connections can also introduce contamination risks, especially downstream of the sterilizing filter. In more manual setups, operator dependency becomes a real factor, and achieving reliable wetting can be trickier than it sounds.
“On top of that,” he continues, “more complex assemblies come with typical engineering challenges: dead legs, hold-up volumes, or simply designs that are harder to keep compliant. So, while the regulatory acceptance is clearly there, many organizations are still refining how to implement PUPSIT in a robust and efficient way.”
And technology—specifically single-use systems—is key to this refining process.
“There’s a clear trend toward single-use, preassembled flow paths, which help reduce handling and variability. At the same time, integrity testing technologies are evolving, both in terms of sensitivity and integration.
“Solutions that can assess not just the filter, but the system as a whole, are becoming increasingly relevant. Ultimately, it comes down to combining good engineering with reliable, well-validated procedures,” Glanz says.
Future
The emergence of automated testing systems is also likely to increase biopharma industry use of PUPSIT, according to Glanz.
“The benefits are quite tangible: automated wetting, venting, and testing steps; tighter control over process parameters; fewer manual interventions, particularly on the sterile side; and improved repeatability.
“Automation also enables better documentation, with electronic records and audit trails integrated directly into the system. In a way, this shifts the focus from operator execution to system design and validation, which aligns well with current regulatory thinking,” he says.
The post Innovative Tech Testing in Response to GMP Revisions appeared first on GEN – Genetic Engineering and Biotechnology News.
GLP-1s May Benefit Mental Health Through Gut–Brain Axis
GLP-1 drugs could act on depression by improving the balance of microorganisms in the intestinal tract, preclinical research suggests.
The findings, in Cell Host & Microbe, suggest extra benefits from this new class of drugs, beyond their metabolic effects on diabetes and obesity.
The GLP-1 receptor agonist liraglutide appeared have mental health benefits on mice, influencing brain function and behavior and reducing symptoms of depression.
This related to an increase in the abundance in the microbe Lactobacillus delbrueckii, which is known to act positively on neurons relating to stress.
Researcher Yonggui Yuan, PhD, from Southeast University in Jiangsu, China, noted mixed results from previous studies into the antidepressant effects from GLP-1 agonists.
“The prevailing model held that these drugs act directly on GLP-1 receptors in the brain, while our study provides evidence for an alternative pathway,” he said.
Emerging evidence suggests this drug class may exert biological effects beyond GLP receptors, such as reducing neuroinflammation after stroke or protecting against cisplatin-induced kidney injury.
The researchers therefore examined the neuropsychiatric effects of liraglutide and found that it had antidepressant effects that remained in mice deficient in the GLP-1 receptor.
The team identified a pathway independent of the GLP-1 receptor through which liraglutide could alleviate depressive-like behaviors in the animals.
Liraglutide encouraged the growth of L. delbrueckii by improving bacterial biosynthesis of serine and phosphoenolpyruvate (PEP), two metabolites that occupy pivotal roles in bacterial central metabolism.
PEP serves as a precursor for biosynthesis of amino acids, nucleotides, and cell wall components while the amino acid serine is a key node in one-carbon metabolism and a precursor for glycine, cysteine, and phospholipid synthesis, all essential for rapid bacterial proliferation.
Increasing levels of L. delbrueckii aided the production of diacylglycerol via triacylglycerol lipase.
This provided a precursor by which the animals could synthesize 2-arachidonoylglycerol (2-AG) levels, to normalize neuronal activity in emotional brain regions.
Gut-derived 2-AG inhibited stress-induced neuronal hyperactivity in the basolateral amygdala and dorsomedial hypothalamus, revealing a microbiota-endocannabinoid axis for potential use in depression therapy.
“Given the growing clinical use of GLP-1R agonists for metabolic disorders and the high comorbidity between metabolic and psychiatric conditions, understanding these pleiotropic, microbiota-mediated effects has important translational implications,” the authors noted.
“More broadly, the demonstration that a clinically approved metabolic drug can exert neuropsychiatric effects through microbiota-dependent mechanisms opens new avenues for drug repurposing and suggests that the therapeutic potential of existing pharmacological agents may extend far beyond their originally intended targets,” the authors concluded.
The post GLP-1s May Benefit Mental Health Through Gut–Brain Axis appeared first on Inside Precision Medicine.
OB-GYN association, deviating from CDC guidance, issues its own vaccine recommendations
The American College of Obstetricians and Gynecologists has released a recommended vaccine schedule for pregnant people, one that diverges from the advice currently offered by the Centers for Disease Control and Prevention.
ACOG is recommending four vaccines be routinely administered during pregnancy, with several other vaccines recommended under certain circumstances. The new schedule is endorsed by 13 medical societies and health organizations.
Phase Ib/IIa for Hepatitis B Epigenetic Silencer Shows Best-in-Class Potential
When John McHutchison, MD, the former head of research and development at Gilead and a leading figure in hepatitis virus therapeutics, saw Tune Therapeutics’ preclinical data on sustained epigenetic silencing of the hepatitis B virus (HBV), he knew it was time for a major pivot.
“When I saw the Tune data on the long-term silencing of an infected cell line for 500 days, I realized it had never been seen before,” McHutchison told Inside Precision Medicine. “I was at Gilead for ten years, where I was head of research and development and worked on all the other viruses, including hepatitis C (HCV)… We spent a decade at Gilead trying to silence this mechanism without success.”
McHutchinson decided to get plugged into Tune Therapeutics, which was founded by Akira Matsuno, Charles Gersbach, PhD, and Fyodor Urnov, PhD, to develop epigenetic therapies that precisely control gene expression without altering DNA sequences. In January 2023, McHutchinson joined Tune’s board of directors and, two years later, became CEO and chairman in March 2025. That preclinical silencing has now shown promise in translating to the clinical setting.
Last month at the European Association for the Study of Liver (EASL) Congress in Barcelona, Spain, Tune presented the first clinical evidence of epigenetic silencing in HBV. The Phase Ia/IIb clinical data shows deep and durable antiviral activity, including silencing of both the integrated virus and covalently closed circular DNA (cccDNA)—a stable viral mini-chromosome that resides inside liver cell nuclei and continually produces new virus particles—offering a possible pathway to a lasting therapeutic effect for HBV patients.
“Now we have the data that shows we can durably silence a gene of interest in humans by modulating epigenetics without cutting,” McHutchison said. “That’s a big deal. The de-risking of the technology.”
Swimming upstream
More than 240 million people worldwide live with chronic HBV infection. Current antiviral therapies can suppress viral replication for years, sometimes decades, but they rarely eliminate the virus entirely. Once treatment stops, viral replication almost always returns. The central problem is cccDNA, often referred to as HBV’s “molecular reservoir,” which acts as a stubborn, self-renewing blueprint, making chronic HBV highly difficult to eradicate or cure.
“It’s also not lost on me that for a decade, our industry has poured billions of dollars into HBV, but without success,” said McHutchinson. “Why is that? Why didn’t we get there? Because we weren’t transcriptionally silencing the reservoir. We were working downstream.”
McHutchinson points out that even the most recent genetic medicines that have shown promise, such as the experimental HBV drug, an antisense oligonucleotide (ASO) called bepirovirsen developed by GSK, still work downstream. Bepirovirsen does not eliminate HBV’s reservoir of cccDNA inside liver cells. Instead, it targets and destroys HBV RNA transcripts, reducing viral replication and lowering the production of viral proteins such as HBsAg, while also helping restore immune responses against infected cells. Because the drug leaves cccDNA intact, its goal is not a cure at the genetic level but instead a functional one, where the immune system keeps the virus permanently suppressed or undetectable after treatment ends.
“You’d silence reverse transcription or cut it with siRNA, and things would fall in the serum, but you wouldn’t affect the reservoir,” said McHutchinson. “As soon as those drugs were removed, the reservoir started to make new viruses again. Nobody is, in essence, being cured. But here we’re working upstream, where the progeny and the new virus are being made.”
GSK may not see eye to eye with McHutchinson on bepirovirsen, which, according to a recent press release, “achieved functional cures in 19% of participants in two large Phase III trials when added to standard antiviral treatment for six months.” Chronic hepatitis B (CHB) is considered “functionally cured” when the blood has no detectable hepatitis B surface antigen or virus DNA for at least 24 weeks after a finite treatment course, allowing immune control without medication and reducing the risk of liver complications, including liver cancer, and all-cause mortality.
However, to McHutchinson, a functional cure and a genetic cure are apples and oranges. “That’s just stimulating an innate immunity,” he said. “It’s an injection a week for 24 weeks, and it’s an ISO that stimulates innate immunity—that’s why it’s curing one in five people who have low levels of HBV surface antigens. It’s a positive development for the field that something else could be approved. I speak admirably about that. But it’s not a panacea. And there’s a lot of room for many other people to come along with better things and better combinations.”
Durable biomarker suppression
Tune’s ongoing Phase Ib/IIa trial includes four dose levels of its therapy, administered as a single intravenous infusion, in 19 people. The dose cohorts ranged from 0.2 mg/kg to 0.85 mg/kg, as well as a multiple-dose cohort receiving up to three infusions. Another seven people got up to three infusions of the second-highest dose given at least four weeks apart, for a total of 26 participants, which McHutchinson acknowledged is quite small.
According to Tune, antiviral activity was seen across all major HBV biomarkers, including surface antigen (HBsAg), pregenomic RNA (pgRNA), e-antigen (HBeAg), HB core-related antigen (HBcrAg), and phosphorylated HBV core antigen. Tune reported that biomarker repression occurred in 100% of participants treated at dose levels two through four. Particularly striking were signs suggesting direct cccDNA silencing. Among HBeAg-negative patients treated at higher dose levels, four of seven lost detectable pgRNA, while three of those patients also lost HBcrAg. In HBeAg-positive patients, three of five lost detectable HBeAg.
McHutchison emphasized that the most encouraging signal may be durability. “Some of those patient graphs we showed have durability up to 250 or 300 days,” he said. “These genes have plateaued at very low levels and haven’t come back with a single application, which suggests and proves what we thought preclinically—that the methylation fingerprint and chromatin compaction are durable and don’t seem to leak or relapse.”
According to the company, suppression following a single dose has now been observed for as long as 17 months in some patients. As with any first-in-class therapy, safety remains a major focus. So far, Tune says TUNE-401 has shown a “favorable safety profile,” with mild to moderate infusion-related reactions, transient liver enzyme elevations, and temporary platelet reductions that resolved without major complications. “We have an acceptable and good safety profile compared to others,” McHutchison said. “What we are seeing in terms of AST and ALT elevations, infusion-related reactions, and transient reductions in platelets are pretty much in line with or better than what others are seeing with similar LNP products.”
Importantly, the company says it has not yet observed additive toxicity in patients receiving multiple doses. Whether multiple doses will ultimately be necessary remains uncertain. “There are examples in the presentation of a profound effect with a single dose and another patient who showed benefit from a second dose,” McHutchison said. “That’s still to be determined.”
Tune plans to continue dose optimization in Phase II, including testing additional multidose regimens and potentially escalating to even higher doses. “We’re tinkering with the maximum dose, trying to optimize it while keeping safety in mind,” he said.
Diversity, in patient and virus
The technology underlying TUNE-401 sits at the intersection of gene therapy, RNA therapeutics, and epigenetics. Rather than editing DNA permanently, the therapy uses a methyltransferase enzyme and the KRAB domain chromatin-compacting protein module to alter the epigenetic state surrounding HBV DNA.
“Once you’ve laid down that pattern, it is permanent and inheritable through cell division,” McHutchison explained. “We can vary the degree of silencing with our platform: 30%, 50%, 80%, or 100%. For hepatitis B, we tried for complete suppression.”
The concept of epigenetically programming cells has attracted growing interest across biotechnology, particularly as concerns remain about irreversible DNA editing approaches. “We feel, because we’re not editing, we can go after common diseases,” McHutchison said. “We’re looking at cardiovascular targets and a diabetes program as well. That’s what the technology can do without editing. But you have to get it there potently and safely.”
One of the key questions moving forward is whether the therapy will work consistently across the enormous genetic diversity of HBV strains worldwide. The current study spans sites in New Zealand, Hong Kong, and Moldova, intentionally capturing ethnically and geographically diverse patient populations. “There is viral diversity across various geographical areas, probably due to evolution and migration patterns over thousands of years,” McHutchison said. “We’ll be able to look at responses according to genotype.”
Tune estimates its targeting system covers approximately 98.5% of known HBV sequence variants based on historical databases. However, the company acknowledges that some patients in lower-dose groups showed weaker responses, raising questions about viral sequence variability. “We’ll be looking at whether there was a mutation or sequence difference from our target,” McHutchison said. Those analyses are expected later this year as additional viral sequencing data becomes available.
Addressing the applicability of TUNE-401 in diverse populations of people and viruses depends on something that Tune hasn’t yet got—numbers. That’s where GSK’s bepirovirsen holds a massive edge, with the two Phase III efficacy trials having involved more than 1,800 participants in 29 countries. The trial for TUNE-401 reported data from about 1–2% of GSK’s entire cohort.
A potential turning point
For McHutchison, the development path may resemble the evolution of HCV treatment, where he played a central role during his years at Gilead. He points to Pharmasset and the development of sofosbuvir (Sovaldi), a direct-acting nucleotide analog that blocks the virus’s essential protein (NS5B polymerase), which became the backbone of curative HCV regimens. “People forget that Sovaldi didn’t work that well by itself initially,” McHutchison said. “It had to be combined with ribavirin and interferon. But it was the backbone mechanism. I think in essence we have that backbone mechanism here.”
TUNE-401 could serve as the foundation for combination regimens capable of delivering a total remission from HBV. The company plans to initiate a larger Phase II study as early as late 2026, exploring combinations alongside optimized dosing schedules. “The approval endpoint for a finite HBV therapy is to drive these biomarkers negative, remove background therapy, and make sure people don’t relapse,” McHutchison said.
Many hurdles remain before TUNE-401 could approach regulatory approval. The current data comes from a small early-stage trial, long-term durability remains unproven, and the field has seen many HBV programs falter after initially promising signals. Still, the idea of directly silencing cccDNA—rather than merely suppressing downstream viral activity—represents a conceptual shift that many hepatologists have sought for decades.
“Over the prior 30 years in hepatology, I have rarely seen a clinical signal this clear,” McHutchison said.
The company’s broader ambitions extend beyond infectious disease. Tune has previously disclosed programs in cardiovascular disease and type 1 diabetes, where epigenetic modulation could potentially alter cellular function without permanent genomic changes. Still, HBV offers perhaps the clearest proving ground for the platform because the virus depends so heavily on transcriptional activity from cccDNA.
Whether Tune’s epigenetic editing approach succeeds remains uncertain. But for a field long defined by incremental advances and repeated disappointments, the data presented in Barcelona may represent something increasingly rare in HBV research: a plausible new path towards a cure.
And for McHutchison, it closes a loop that began years earlier in Gilead’s hepatitis research labs. “We knew this mechanism mattered,” he said. “The technology just didn’t exist yet. Now it does.”
The post Phase Ib/IIa for Hepatitis B Epigenetic Silencer Shows Best-in-Class Potential appeared first on Inside Precision Medicine.
STAT+: Hope for Kendall Square’s lab market
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Good morning. In today’s news, we have: pricing conundrums, lab demand, and drug shortages.
The need-to-know this morning
- Sanofi said it was halting a Phase 3 study of its drug riliprubart in a rare autoimmune disease after an interim analysis showed the therapy was not effective. It’s the latest blow to the French firm’s R&D efforts, which new CEO Belén Garijo has been brought in to revitalize.
- Parabilis Medicines, a developer of cancer medicines, raised $670 million in an initial public offering. It’s the largest-ever biotech IPO, topping obesity drugmaker Kailera Therapeutics’ $625 million debut in April.
European countries at odds over drug-pricing policies
In Europe, countries are grappling with what to do about drug prices as they contend with conflicting pressures. Aging populations and growing rates of chronic disease are straining their budgets, but, at the same, the U.S. and drugmakers are demanding they pay more for medicines.
<![CDATA[AbbVie’s short-acting psychedelic bretisilocin shows rapid MADRS drops in phase 2a MDD trials, hinting at scalable, supervised depression care.]]>
mRNA Tails Play Key Role in Folding Regulatory Proteins
mRNA 3′ UTRs have hundreds of highly conserved nucleotides, but their biological roles are unclear. In a new study published in Cell titled, “mRNA 3′ UTRs chaperone intrinsically disordered regions to control protein activity,” researchers from Memorial Sloan Kettering (MSK) Cancer Center now demonstrates that mRNA 3′ UTRs play a key role assisting the folding of regulatory proteins.
“The traditional view is that only specialized proteins act as ’chaperones’ to help other proteins fold correctly,” said Christine Mayr, MD, PhD, a member of the Sloan Kettering Institute and corresponding author on the paper. “Our research shows that RNA can do this, too—and that mRNAs act as their own chaperones for a group of important, hard-to-fold proteins.”
While 3′ UTRs have traditionally been dismissed as key regulators, Mayr emphasizes that thousands of human 3′ UTRs have highly conserved sequences across vertebrates, offering a clue of their function. “Biology doesn’t usually preserve things that aren’t needed,” she says.
Many larger, complex regulatory proteins, such as the transcription factors MYC, UTX, and JMJD3, possess long, flexible regions, named intrinsically disordered regions (IDRs), that do not fold into stable structures on their own.
The study showed that cells solve this folding problem using specialized compartments, known as mesh-like condensates. The 3′ UTR promotes IDR–IDR interactions and suppresses folding between domains. Results suggest that this chaperone activity prevents interference between hydrophobic clusters in the IDR with folding of the structured domain.
The team identified more than 2,700 genes with highly conserved 3′ UTRs, or about one in every eight protein-coding genes in the human genome. The proteins expressed by these genes contain intrinsically disordered regions that require RNA chaperones to facilitate folding.
“What we show is that for thousands of regulatory proteins in human cells, the genetic code alone isn’t enough to make a functional protein—you need the RNA chaperone too,” said Mayr.
The study has practical implications for laboratory research. For thousands of regulatory proteins, removing the 3′ UTR allows researchers to study the misfolded, and less active version of the protein.
The post mRNA Tails Play Key Role in Folding Regulatory Proteins appeared first on GEN – Genetic Engineering and Biotechnology News.