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14 published stories · Gene Therapy

Gene Therapy

New RNA upgrades make prime gene editing highly efficient

Prime editing is a highly precise genetic tool that allows scientists to rewrite DNA without making dangerous double-strand breaks in the genetic code. To do this, the system relies on a guide molecule made of RNA, which acts like a biological GPS to find the exact spot in the genome that needs fixing. However, these RNA guides are fragile and can break down inside cells before they finish the job. To protect them, scientists attach tiny stabilizing structures, known as motifs, to the end of the RNA guide. To find the best possible stabilizers, researchers developed a new high-throughput testing system called PE-PRISM. This tool allowed them to rapidly screen 2,858 different RNA motifs inside human cells. Through multiple rounds of testing and optimization, the research team identified three engineered winners named tevo2.0, eHAV, and eSBRMV1-A. When put to the test, these newly upgraded motifs completely outperformed the current standard stabilizer. In experiments designed to correct hundreds of disease-associated genetic mutations, the top new motifs proved more efficient than the older version over 90 percent of the time. The researchers successfully used these stabilized guides to correct mutations in human cells as well as inside the brains and livers of living mice.

Nature Biotechnology · 2 min read

Gene Therapy

Tiny Typos in Gene-Editing Materials Pose Hidden Risks

When scientists use gene-editing tools like CRISPR to fix disease-causing DNA, they often use a customized genetic template to guide the repair. These templates, called single-stranded oligonucleotides, are synthesized in laboratories and act like a molecular blueprint, showing the cell exactly how the corrected DNA should look. But new research reveals a hidden problem. The laboratory-made blueprints themselves often contain tiny manufacturing typos. Researchers tested templates from three different manufacturers and found synthesis errors in all of them. Alarmingly, when cells use these flawed templates during a natural genetic fix known as homology-directed repair, they copy the mistakes directly into the genome. The study showed that the frequency of these errors being permanently pasted into a cell's DNA matches how often the typos appear in the manufacturer's template mixture. To see how this might play out in practice, the team looked at an experimental gene-editing protocol designed to cure sickle cell disease. They found that while some typos created harmless variations, certain missing letters created new, harmful mutations predicted to cause a different blood disorder called beta-thalassemia. It is important to note that these findings are currently based on laboratory testing of three manufacturers and one specific sickle cell protocol, meaning the exact risk levels may vary across different experimental treatments.

bioRxiv · 2 min read

Gene Therapy

Gene-edited stem cells program the immune system to fight disease

Our immune system relies on B cells to act as tiny factories, churning out antibodies to fight off infections. But for some viruses, like HIV, our bodies struggle to make the right antibodies naturally. Scientists have developed a potential workaround. By taking blood-forming stem cells, known as hematopoietic stem and progenitor cells, and editing their genes, researchers were able to program these cells to produce highly effective therapeutic antibodies. In a recent study using mice, researchers engineered these stem cells to carry the instructions for a powerful antibody that neutralizes HIV. When they transplanted just a few hundred of these edited cells into the mice, the cells settled in and became B cell precursors. After the mice were exposed to an HIV protein, these customized immune cells multiplied and produced high levels of the protective antibody. When the antibody levels eventually started to drop, a simple booster shot kept the production going strong for at least nine months. The technique proved highly adaptable. Researchers found they could mix different batches of engineered cells to produce multiple antibodies at once, creating a multilayered defense against HIV. They also successfully programmed cells to fight off malaria and influenza, with the flu antibodies protecting the mice from what would have been a lethal infection. Importantly, this is an early-stage proof of concept. The experiments have only been conducted in mice, requiring much more research before we know if it will work in humans.

Nature Biotechnology · 2 min read

Gene Therapy

A Remote Control for Genes Powered by Electromagnetic Fields

Imagine being able to turn a specific gene on or off simply by flipping a switch, much like controlling a lightbulb. This kind of "gene switch" is a crucial tool for scientists looking to control when and where genes are active inside a living body. Traditionally, these switches have relied on chemical drugs to activate them, which can sometimes trigger unintended side effects or lack precise timing. Now, researchers have developed a completely new kind of switch that is controlled remotely by electromagnetic fields. To build this non-invasive system, the scientists engineered a special piece of DNA called a promoter, which acts like a starter engine for a specific receptor known as LGR4. They discovered that a cellular protein called cytochrome b5 type B acts as a tiny antenna that senses the electromagnetic field. When exposed to these fields, this protein causes calcium to flood into the cell. This sudden rush of calcium is the biological signal that tells the target gene to turn on and start working. The research team tested this system in living mice. By changing the animals' exposure to the electromagnetic fields, they were able to strongly increase or decrease the activity of targeted genes within a three-day timeframe. However, this technology is still in its very early stages. So far, the switch has only been successfully tested in mouse models, meaning much more research is needed before we know if it can be safely and effectively translated for human application.

Nature Biotechnology · 2 min read

Gene Therapy

First inside-the-body CRISPR gene therapy heads to the FDA

Intellia Therapeutics is making medical history as it seeks approval from the US Food and Drug Administration for a groundbreaking genetic treatment. The drug, called lonvoguran ziclumeran or lonvo-z, is the first CRISPR-based gene therapy designed to work "in vivo," meaning the genetic editing happens directly inside the human body. CRISPR is a biological tool that allows scientists to make precise changes to DNA. Intellia is using this technology to treat hereditary angioedema, a genetic condition that causes severe and unpredictable swelling attacks. The company recently completed a Phase 3 clinical trial, which is the final testing step before seeking regulatory approval. In the study, a single dose of lonvo-z reduced swelling attacks by 87 percent compared to a placebo over a six-month period. Even more strikingly, 62 percent of the patients who received the treatment had absolutely no attacks during those six months and were able to completely stop taking their usual preventative medications. While these numbers are highly encouraging, the research does come with a few early caveats. The trial was relatively small, involving a total of 80 patients, with 52 receiving the actual therapy and 28 given a placebo. Additionally, the currently reported results only track the patients for six months. Researchers will need to monitor these individuals for a longer period to confirm that the single dose continues to work safely and effectively over time.

Nature Biotechnology · 2 min read

Gene Therapy

Promising Gene Therapy Hits a Regulatory Roadblock

Regenxbio recently shared encouraging results from a late-stage clinical trial for a new gene therapy aimed at treating Duchenne muscular dystrophy. This severe condition causes progressive muscle weakness. The experimental treatment, called RGX-202, is designed to help the body produce a crucial muscle-protecting protein called microdystrophin. In the recent study, 28 out of 30 evaluated patients successfully reached target levels of this important protein. Despite these positive biological signs, the path forward is complicated. About 6.5 percent of patients in the trial experienced serious side effects linked to the treatment, including heart inflammation and asymptomatic liver injury. Fortunately, these issues were safely resolved without causing any lasting damage. Still, the FDA has recommended that the company conduct a randomized controlled trial. This rigorous type of study compares the new treatment against a placebo or standard care, and completing it could delay the therapy's market approval until 2030. A major reason for the FDA's caution is that without a randomized trial, it remains unclear how much the therapy actually improves a patient's daily physical function. Medical experts also note a common limitation with new medical breakthroughs: once a drug is approved for broader public use outside of carefully monitored trials, unexpected safety issues can sometimes emerge.

GEN · 2 min read

Gene Therapy

New Platform Promises to Streamline Gene Therapy Production

The biotechnology company VIVEbiotech has introduced a new system called EvoLVcell, which is designed to upgrade how scientists manufacture lentiviral vectors. In the world of gene therapy, lentiviral vectors act as microscopic delivery vehicles that carry helpful genetic material directly into a patient's cells. Creating these delivery vehicles is traditionally a highly complex and sensitive process, but this new platform aims to make it significantly easier. Typically, making these vectors requires a step called transfection, where scientists use specialized chemicals and extra pieces of DNA known as plasmids to force cells to produce the desired viral vectors. EvoLVcell removes this step entirely by using what is known as a stable producer cell line. This means the laboratory cells are already permanently equipped with the instructions needed to manufacture the vectors. By skipping transfection, manufacturers no longer have to depend on the unpredictable supply chains for plasmids and chemical reagents. According to the company, taking this streamlined approach comes with several practical benefits. It reduces the unpredictable variations that often occur from one batch of vectors to the next, lowers the amount of unwanted impurities, and improves the overall quality of the final product. Furthermore, the platform works quickly, allowing drug developers to generate a working prototype cell line and evaluate their production yields in just three months.

GEN · 2 min read

Gene Therapy

Gene and RNA Therapies Rebound with a Surge in Startups and New Targets

The field of genetic medicine is experiencing a significant resurgence. According to a recent industry report, worldwide approvals have now reached 42 gene therapies, 38 RNA therapies, and 76 cell therapies that are not genetically modified. This clinical success is mirrored by a rebounding business landscape. In the first quarter of the year, 26 new startup companies were formed in this sector, a number that sits well above the historical average of five to twenty. Alongside this growth, researchers are shifting their focus toward a wider variety of diseases. While these advanced treatments have historically been associated with fighting cancer, over 60 percent of current gene therapy clinical trials are now targeting non-cancer conditions. In the realm of RNA medicine, a fascinating split is occurring. Therapies based on RNA interference (a technique known as RNAi that helps silence faulty genes) are seeing strong pipeline growth. On the other hand, therapies using messenger RNA (mRNA, which gives cells temporary instructions to make proteins) are actually experiencing a decline quarter over quarter. Despite these promising signals, it is important to note that most of this research is still in its infancy. While the overall pipeline of potential new medicines is massive, the vast majority of these assets remain in the earliest stages of human testing. Currently, there are 669 gene therapy trials in Phase I or Phase II (the initial stages to check safety and basic effectiveness) compared to only 41 trials that have made it to the final Phase III stage.

GEN · 2 min read

Gene Therapy

Novel Gene Therapy Shows Early Promise for Delaying Huntington's Disease

Latus Bio, a biotechnology company, is developing a new gene therapy for central nervous system disorders, starting with Huntington's disease. Their lead candidate, called LTS-201, relies on a newly designed delivery vehicle. In gene therapy, scientists often use harmless, modified viruses known as adeno-associated viruses, or AAVs, to carry treatments directly into cells. The researchers identified a specific outer shell of the virus, called a capsid, that excels at this task. Named AAV-DB-3, this new capsid successfully delivered genetic material deep into the brain cells of monkeys using just a single, low-dose infusion per brain hemisphere. Once inside the brain, the therapy works by targeting a specific DNA repair protein called MSH3. In Huntington's disease, certain repeating DNA sequences abnormally expand over time and cause cellular damage. To stop this, the therapy uses an artificial microRNA, which is a tiny molecule specially designed to dial down the production of the MSH3 protein. By lowering the levels of this protein, the researchers aim to reduce these harmful DNA expansions and delay the onset of the disease. The early results are highly encouraging but still in the laboratory testing phase. In animal studies, the treatment reduced MSH3 levels by 50 percent in specialized mice and by 48 to 94 percent in non-human primates. However, it is important to note that this research is strictly in its preclinical stages and has not yet been tested in humans. The company plans to submit an Investigational New Drug application, a necessary step before human clinical trials can begin, in the second half of 2026.

GEN · 2 min read

Gene Therapy

Gene Therapy Linked to Rare Brain Tumor in a Single Patient

For decades, doctors have used harmless viruses known as adeno-associated viruses, or AAVs, as biological delivery trucks to treat genetic diseases. These viruses are engineered to carry healthy genes directly into a patient's cells. But a newly published study reveals an unexpected complication. Researchers recently linked a specific brain tumor in a five-year-old boy to an AAV9 gene therapy he received as an infant to treat an inherited disorder called MPS1 deficiency. When the boy was five, doctors discovered a rare neuroepithelial tumor in his brain. By sequencing the genetic material of the mass, scientists found that the gene therapy payload had accidentally woven itself into the boy's own genome. Specifically, the viral delivery cassette fused with a human gene called PLAG1, which is known to drive tumor growth. Curiously, the tumor also contained a stray fragment of a different human chromosome, which researchers suspect was a manufacturing contaminant from when the viral vector was created. Thankfully, the story has a positive outcome so far. Surgeons successfully removed the tumor. Eight months after the operation, the patient shows no signs of the tumor returning and is actually demonstrating advanced cognitive development.

GEN · 1 min read

Gene Therapy

Scientists Unveil a Compact AI-Designed Alternative to Cas9

Gene editing tools like CRISPR are incredible, but the standard tool, Cas9, is quite bulky. This makes it hard to pack into the tiny delivery vehicles used in gene therapy. Now, researchers have used artificial intelligence and detailed 3D molecular mapping to engineer a much smaller alternative called M82. The team took a naturally occurring enzyme called Cas12l and used an AI language model to predict the best structural tweaks. In early lab experiments on human cells, the resulting M82 variant was highly effective. It achieved a 67.4 percent basic editing rate, matching the industry standard Cas9. Even more impressively, M82 outperformed Cas9 in a more complex type of editing called homology-directed repair, where a new piece of genetic code is smoothly inserted into the DNA. In preliminary tests, M82 successfully inserted genes 39 percent of the time. However, this technology is still in the early preclinical phase and requires testing in living organisms to confirm its real-world safety and effectiveness.

GEN · 1 min read

Gene Therapy

Promising Duchenne Gene Therapy Eyes 2027 FDA Approval Amid Safety Hurdles

Researchers are evaluating a new experimental treatment called RGX-202 for Duchenne, a severe and progressive muscle disease. Developed by the biotechnology company Regenxbio, this gene therapy aims to help the body build a crucial muscle-protecting protein called microdystrophin. To do this, scientists use a modified virus as a microscopic delivery vehicle to insert new genetic instructions into a patient's cells. Compared to existing options, RGX-202 uses a different viral delivery system, produces a larger version of the microdystrophin protein, and is paired with a unique regimen of immune-suppressing drugs. The latest clinical trial results show striking biological changes in patients. Researchers originally set a target for the therapy to restore microdystrophin levels to just 10 percent of normal. Instead, patients receiving the treatment achieved an average of 71 percent expression. Furthermore, the company reported a statistical connection between these high protein levels and a measurable impact on the overall trajectory of the disease. Despite these encouraging signs, the research is still in an early phase with notable limitations. The data comes from an expanded single-arm study, meaning all participants received the active drug and were not compared directly against a control group taking a placebo. The therapy also carries safety risks. Researchers reported two serious adverse events during the trial, which could complicate the treatment's journey to the clinic when compared to existing therapies.

BioPharma Dive · 2 min read