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DNA barcoding reveals which gene-therapy nanoparticles reach targets in vivo

Drug delivery researchers have vastly improved the potential of genetic therapies by overcoming the challenge of consistently getting genes and gene-editing tools where they need to be within cells. Findings of the study spearheaded by Oregon State University College of Pharmacy graduate student Antony Jozić are published in Nature Biotechnology.

When gene therapies enter a cell, they are often sent to lysosomes, the cell’s trash and recycling centers, where therapeutic genetic material is broken down before it can work. For gene therapies to succeed, they must avoid disposal and reach the part of the cell where they can function.

PV inhibitory neurons, not overall prefrontal cortex decline, linked to cocaine-seeking relapse

Drug addiction carries an extremely high risk of relapse, as cravings can be reignited by minor stimuli even long after one has stopped using. Previously, this phenomenon was attributed to a decline in the function of the prefrontal cortex (PFC), which regulates impulses. However, a joint international research team has recently revealed that the cause of addiction relapse is not a simple decline in brain function, but rather an imbalance in specific neural circuits.

Google AI rivals radiologists in breast cancer detection

New research on 175,000 women—the largest NHS study to date—on the use of AI in breast cancer screening shows that AI detected more cases of invasive cancer, more cases overall, had fewer false positives, and recalled fewer women having their first scan than humans did. For one part of the study, AI reduced the time spent reading scans by almost a third.

Resident Macrophages Play a Role in Maintaining Murine Intraocular Pressure

Through their study, the researchers tracked fluorescently tagged resident tissue macrophages in mouse eyes. When they selectively removed these cells, the eye’s drain, or outflow, became clogged, fluid built up, and eye pressure increased.

The discovery could lead to the development of future glaucoma treatments. The next step will be research to identify these resident macrophages in human eye tissue. “This research helps us understand the role of the immune system in regulating eye pressure,” said Katy Liu, MD, PhD, assistant professor in the department of ophthalmology at Duke University School of Medicine. “Our findings show that resident macrophages are essential for maintaining healthy eye pressure,” said Liu. “Disruption of this system may contribute directly to the development of glaucoma.”

Added W. Daniel Stamer, PhD, the Joseph A.C. Wadsworth Distinguished Professor of Ophthalmology, and co-vice chair for basic science research, “Now we have a specific target for developing new therapies that can normalize the eye pressure and stop vision loss, in contrast to current medications that do not target the source of disease.”

Performance characteristics of genome-sequencing–based CHIP calling and impact on epidemiologic associations

Do we need better ways to detect clonal hematopoiesis of indeterminate potential (CHIP)?

In this Research Letter, Alexander G. Bick & team find epidemiology studies underestimate the strength of the association between clonal hematopoiesis and disease due to false negatives from shallow, whole-genome versus deep targeted sequencing.


Address correspondence to: Alexander Bick, 2,200 Pierce Ave., 550 RRB, Nashville, Tennessee, 37,232, USA. Email: [email protected].

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1Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Mining the dark transcriptome: Synthesizing the first potential drug molecules from long noncoding RNA

A team from University of Toronto Engineering is the first to synthesize long noncoding RNA (lncRNA) outside the cell—a new approach to drug discovery that has already yielded some promising anti-inflammatory molecules. The team was inspired by advances in the field of messenger RNA (mRNA) and protein replacement therapies. They realized that a similar approach could be used to deliver lncRNA to the body, unlocking a potential new source of drugs.

“Only about 25% of our DNA encodes for proteins, including everything from insulin for regulating blood sugar to antibodies for immune defense,” says Professor Omar F. Khan, senior author on a paper published in Science Signaling that describes the new discovery.

“Proteins are made via messenger RNA, or mRNA, which conveys the instructions for how to build proteins from our genes to our ribosomes, the part of our cells where proteins are assembled.”

Miniature laser technology could bring lab testing into your home

A research team at Chalmers University of Technology, Sweden, has developed new laser technology that could lead to tiny, cost-effective biosensors. The sensors integrate lasers and optics together on a centimeter-sized chip, which could move testing from hospitals to patients’ homes. This, in turn, would free up hospital beds and reduce visits to clinics.

The team’s study, “Flat Plasmonic Biosensor with an On-Chip Metagrating-Integrated Laser,” is published in ACS Sensors.

By studying how various biomolecules interact with each other—for example, antibodies in the immune system and xenobiotic antigens—researchers can gain valuable insights leading to new medicines and vaccines or assess whether a sample contains signs of infection.

Highly efficient expression of DNA-peptide conjugates in growth-arrested cells

Mohamedshah et al. present an enzymatic strategy for covalently linking nuclear localization sequence (NLS) peptides to DNA cassettes by incorporating a strained cyclooctyne and using SPAAC chemistry, greatly enhancing transfection efficiency compared to previous methods. [ https://www.nature.com/articles/s41467-025-68167-5](https://www.nature.com/articles/s41467-025-68167-5)


Efficient nuclear delivery of DNA remains a major challenge in non-viral gene therapy. Here the authors present an improved workflow for generating DNA oligonucleotide-peptide conjugates which are ligated to linear DNA and achieve nuclear localization.

Focused ultrasound subtly primes human brain to respond, EEG study finds

A research team at Carnegie Mellon University has developed a new noninvasive brain stimulation technique, by showing how focused ultrasound affects the human brain. Using brainwave recordings from human participants, the team found that focused ultrasound can subtly influence brain activity without directly causing neurons to fire. The work clarifies conflicting results in the field and introduces a new approach to noninvasive brain stimulation. The study is published in Nature Communications.

Focused ultrasound has been studied for years, but its effects in humans are not well understood. One challenge is that the technology makes a quiet beeping sound that can trigger hearing pathways in the brain, making it hard to know whether changes are caused by the sound or by the ultrasound itself. Previous studies using MRI scans may also produce misleading signals.

To address these limitations, researchers conducted a resting-state study in 27 human participants using concurrent whole-brain EEG recordings. They compared low-intensity transcranial focused ultrasound (tFUS) alone, a mild electrical brain stimulation called tDCS, and a new approach that combines the two, deemed transcranial electro-acoustic stimulation (tEAS). When used alone, neither ultrasound nor electrical stimulation caused clear, targeted brain responses. However, when combined, they produced strong, specific activity in the targeted area.

Patients with symmetric Parkinson’s disease do poorly with subthalamic stimulation

Patients with symmetric PD can be identified with a simple and straightforward method, a ratio right by left hemibody score equalling 1. This requires no additional time, effort or specialised neuroimaging or laboratory resources.


Background Motor asymmetry is a hallmark of Parkinson’s disease (PD), but ~20% of patients present with symmetric motor signs, which are associated with faster disease progression and poorer dopaminergic response. The impact of motor symmetry on activities of daily living (ADL) outcomes following subthalamic deep brain stimulation (STN-DBS) remains unclear. We hypothesised that patients with symmetric PD experience less ADL improvement post-STN-DBS than asymmetric PD patients.

Methods This was a prospective, quasi-experimental, non-randomised, controlled, international multicentre study with a 6-month follow-up. The primary outcome was the Scales for Outcomes in Parkinson’s Disease-Motor ADL scale. Secondary outcomes included Unified Parkinson’s Disease Rating Scale motor examination and Parkinson’s Disease Questionnaire-8 (PDQ-8). We defined symmetric PD as a right-to-left hemibody motor score equalling 1. We analysed within-group longitudinal changes, between-group outcome differences, effect size and correlations between PDQ-8 and motor changes. We confirmed results in a propensity-score matched subcohort with well-balanced demographic and clinical parameters.

Results We included 200 patients with asymmetric and 54 with symmetric PD. In symmetric PD, ADL remained stable, which was not associated with the observed PDQ-8 improvement. In contrast, in asymmetric PD, ADL improved with a moderate effect size, which correlated moderately with PDQ-8 improvement. In symmetric PD, the absolute risk of experiencing no clinically relevant postoperative ADL improvement was 23.8% higher.

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