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Category: bioengineering – Page 4

Tailored FcγR blockade enhances immune checkpoint therapy and overcomes resistance

Fc-gamma receptors (FcγRs) regulate IgG antibody activity, and Fc-engineering is a proven method to improve the efficacy of tumor-targeting antibodies. Here, we explore tailored FcγR blockade to enhance the therapeutic efficacy and tolerability of immune checkpoint-blocking (ICB) antibodies.

Mechanistically matched murine surrogate and human lead FcγR-blocking and immune checkpoint-blocking antibodies were used to study whether tailored FcγR-blockade, targeting FcγRIIB selectively or all FcγRs, can enhance the efficacy and overcome resistance to immune checkpoint therapy in vivo and in vitro. Mechanistic studies were performed with clinical reagents, including ipilimumab, nivolumab, pembrolizumab, and human FcγRIIB-selective (BI-1607) and pan-FcγR-blocking (BI-1206) antibodies, using human cells and transgenic animals with clinically relevant expression of immune checkpoint receptors.

We demonstrate that FcγRIIB-selective and pan-FcγR-blocking antibodies increase the in vivo efficacy of αCTLA-4 and αPD-1 antibodies, respectively. FcγRIIB-selective antibody enhancement of αCTLA-4 was associated with increased intratumoral Treg depletion, myeloid reprogramming, interferon-γ and CXCL10-induction, and increased activated effector CD8+ T cells, correlating with higher activating-to-inhibitory (A: I) FcγR engagement ratios. Conversely, pan-FcγR blockade protected αPD-1-coated T cells from macrophage phagocytosis, increasing intratumoral activated CD8+ T cells by decreasing activating and inhibitory FcγRs.

AI‑designed gene‑editing enzymes expand the CRISPR toolbox

Scientists have made many advances using traditional CRISPR technology, especially in medicine, but they are now seeking ways to create genuinely new gene-editing enzymes with properties that have not already evolved naturally. A new study, published in Science, describes a new AI-designed synthetic TnpB enzyme, called SynTnpBs, that has outperformed the natural reference enzyme.

Creating new gene editors CRISPR tools use a programmable guide RNA to direct an enzyme to a specific target in the genome to edit (cut, insert or correct) DNA. The TnpB enzyme is a compact ancestor of certain CRISPR enzymes, called CRISPR-Cas12 enzymes. Researchers think its small size could make it useful in situations where delivery space is limited, like some kinds of gene editing in plants. However, these enzymes can be difficult to redesign.

While AI has been useful for automating complex genome editing and predicting DNA repair outcomes, most AI methods used for generating gene-editing enzymes have produced versions that are still very similar to natural proteins. When researchers have attempted to create new editors with novel, useful properties, they have found it challenging to change the protein without breaking the molecular contacts needed for DNA editing.

Gene editing tool reduces Huntington’s toxic protein fragments and symptoms in mice

A gene-editing tool designed to precisely rewrite the gene that causes Huntington’s disease reduced toxic protein fragments and symptoms associated with the disease in mice, researchers at the University of Illinois Urbana-Champaign report.

While other gene-based treatments have focused on turning the gene off, the Illinois team took a different approach. The researchers designed a base-editing tool to alter a specific point in the huntingtin gene so the cell’s machinery would skip over a small section prone to generating toxic fragments while preserving enough huntingtin protein to support its normal functions.

Led by Pablo Perez-Pinera and Thomas Gaj, professors of bioengineering at the U. of I., the researchers published their findings in the journal Nature Biomedical Engineering.

Insect-inspired electronic nose: Turning semiconductor chips into olfactory sensors

Bioengineers at the University of California San Diego integrated the olfactory receptor of an insect called a jumping bristletail into semiconductor chips made of graphene, creating an electronic nose capable of sniffing out a wide variety of small organic compounds. This biomimetic bioelectronic sensor can detect and distinguish between molecules that are difficult for conventional electronic sensors to differentiate. This work opens the door to building semiconductor-based chemical sensing systems inspired by nature for applications in health care, environmental monitoring, food quality, agriculture and biodefense.

In a paper published in Advanced Materials, researchers led by bioengineers at UC San Diego describe a method for manufacturing the MhOR5 odorant receptor from the insect Machilis hrabei at scale and chemically attaching the purified MhOR5 protein to high-performance graphene field effect transistors (gFETs). gFETs are semiconductor devices that rely on graphene instead of silicon as the conductive material, resulting in exceptional sensitivity to molecular changes.

The researchers tested their MhOR5-functionalized gFETs against 16 chemically diverse compounds, including DEET, hexanol and eugenol, at different concentrations. The sensor produced a concentration-dependent electrical response for each of the 16 compounds.

AI finds tiny gene editor changes that reduce unintended DNA edits

Gene editing is a highly precise and powerful technology that allows scientists to insert, delete, modify or replace DNA bases in living organisms. It has a variety of uses, including correcting disease-causing mutations and improving crops. Tools like CRISPR act as molecular scissors that target specific places in a genome to make these changes. But the technology is not perfect and can accidentally edit the wrong pieces of DNA or RNA.

In research published in Nature, scientists describe a new framework that uses AI to make these tools more accurate. Hoi Yee Chu and Alan S.L. Wong of the University of Hong Kong published a News and Views piece in the same journal on the significance of this research.

Inherited gene variants may shape CAR-T therapy benefits and toxic side effects

Chimeric antigen receptor (CAR)-T cell therapy, which reprograms an individual’s immune cells to seek out and destroy certain cancer cells, has revolutionized treatment for blood cancers such as lymphoma. But in some patients, the treatment can cause serious side effects. New research led by investigators at the Mass General Brigham Cancer Institute, the Broad Institute of MIT and Harvard, and Dana-Farber Cancer Institute has shown that patients’ inherited genetic makeup can influence whether they benefit from CAR-T cell therapy or experience toxicity from the treatment. The results are published in Science Immunology.

“These findings have important implications for understanding how CAR-T cells behave in patients since each CAR-T cell product is unique to the person from whom it is manufactured, unlike all prior forms of therapy, which are identical across patients,” said lead author Mark B. Leick, M.D., an oncologist at the Mass General Brigham Cancer Institute.

For the study, Leick and his colleagues sequenced the entire genomes of more than 200 patients with aggressive lymphoma from two major clinical trials of CAR-T cell therapy. In one of the trials, patients with T cells with variants that silenced the STXBP2 gene tended to experience toxicity related to CAR-T cell therapy. Also, donor T cells engineered to lack STXBP2 and/or express these STXBP2-silencing variants triggered inflammation.

Can This New Enzyme Reverse Aging?

This is rather technical.

Researchers at Revel Pharmaceuticals and Calico Life Sciences have engineered CMLase, an enzyme that removes carboxymethyl-lysine (CML) — a glycation product long considered permanent damage on our longest-lived proteins. In this video I explain the details behind this discovery and what it means for the aging field.

Find me on Twitter — / eleanorsheekey.
official website — https://www.thesheekeyscienceshow.com/

Support the channel.
through PayPal — https://paypal.me/sheekeyscience?coun… through Patreon — / thesheekeyscienceshow TIMESTAMPS 0:00 – Intro: what CML is and why it seemed irreversible 2:25 – How they made the enzyme 6:20 – Human tissue data 7:40 – My thoughts and limitations Paper: Trabosh et al., Nature Communications, 2026 — https://doi.org/10.1038/s41467-026-75… note that The Sheekey Science Show is distinct from Eleanor Sheekey’s teaching and research roles. The information provided in this show is not medical advice, nor should it be taken or applied as a replacement for medical advice. The Sheekey Science Show and guests assume no liability for the application of the information discussed. Icons in intro; “https://www.freepik.com/free-photos-v…“Background vector created by freepik — www.freepik.com.
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TIMESTAMPS

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Team uses AlphaFold AI to redesign geneediting proteins to make them safer

A couple of decades after the discovery of systems that could selectively target DNA, we’re starting to see the first therapies based on gene editing. One challenge these developments have faced is safety. While we can make them pretty specific to the gene we want edited, the human genome is very large, and even rare DNA sequences can appear a couple of times by chance.

As a result, all the original gene-editing systems had known rates of what are called off-target effects, in which they simply edit the wrong sequence. This may be a low-probability event, but edit enough cells—and therapies generally have to edit many—and errors become inevitable.

A lot of effort has gone into finding ways to minimize or eliminate off-target edits. In a recent issue of Nature, researchers described modifying the AI protein-folding software AlphaFold to help identify key areas of gene-editing proteins responsible for off-target effects. Those areas were then modified to reduce the problems.

Drug discovery Is changing. Drug development must change too

💬 Artificial intelligence and big data are flooding discovery pipelines with high-potential drug candidates, but this rapid innovation has created a new challenge. Simply put, our capability to design miracle molecules is vastly outstripping our technology to mass-manufacture them safely for the global public. Moving drug making from the scale of lab flasks to commercial bioreactors introduces non-linear biological and engineering shifts that can undermine tasks like purification.

⚡In this New Scientist CoLab podcast, experts from global life sciences leader Cytiva explain the hidden, high-stakes science of purification that is required to close the gap between drug discovery and the pharmacy shelf.

Creating a healthspan digital twin: A new era for humanity to better living — Jul 30

Zahi A. Fayad, PhD, is the Lucy G. Moses Professor of Medical Imaging and Bioengineering at the Icahn School of Medicine at Mount Sinai, where he also serves as Vice Chair for Research in Radiology and holds professorships in Medicine (Cardiology) and AI & Human Health. He is the founding Director of the BioMedical Engineering and Imaging Institute (BMEII), home to one of the nation’s top NIH-funded radiology programs (#2 in 2025 per Blue Ridge rankings). Dr. Fayad also co-leads Mount Sinai’s system-wide Healthspan initiative, coordinating research, clinical, and digital infrastructure to advance precision prevention across the enterprise.

Dr. Fayad is Principal Investigator on multiple major grants, including five NIH-funded projects (3 R01s, 2 P01s) supported by the National Heart, Lung, and Blood Institute, NIAID, and NIDA. A leader in biomedical engineering, his interdisciplinary work integrates advanced imaging, AI, and nanomedicine to drive precision medicine, with research interests focused on how lifestyle stressors — chronic stress, diet, exercise, and sleep — affect long-term cardiovascular and whole-person health.

A Clarivate Highly Cited Researcher since 2018 (~190,000 citations; h-index 142), Dr. Fayad’s seminal contributions include MRI vessel wall imaging (leading to Carotid Plaque-RADS), FDG PET imaging of vascular inflammation, and defining the link between amygdala activity, systemic inflammation, and cardiovascular risk. His research on HDL-based nanoparticles for immune modulation is progressing toward clinical translation for cancer, autoimmune diseases, and transplant rejection — work he is advancing commercially as co-founder of Trained Therapeutix Discovery (TTxD), an early-stage biotech company. He is also a recipient of the Jean Paul II Award for Medicine and Research.

His current projects span cardiovascular, neuroimmune, and transplant-focused research, including stress-induced immune dysregulation; mitral valve prolapse and arrhythmia risk; cocaine use–related carotid atherosclerosis and cognitive impairment; cardiac sarcoidosis therapy monitoring; and immune tracking in organ rejection using nanobiologics — together shifting care upstream toward risk prediction and intervention before clinical events.

He also leads the Mount Sinai DigiTwin Project, an AI-driven platform designed to personalize health optimization by integrating imaging, multi-omics, and real-time physiologic data — initially focused on cardiovascular health and now expanding to whole-person healthspan modeling. Dr. Fayad and colleagues at Mount Sinai are finalists in the $80m XPRIZE Healthspan competition, where they are evaluating a multimodal strategy to meaningfully extend human healthspan.

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