Biology subjects

Manthey, M.

Publications and source records attributed to Manthey, M..

4 recordsLinked to original sources

bioRxiv2025

Adeno-associated viruses escort nanomaterials to specific cells and tissues

The delivery of nanotherapeutics to specific tissues relies on bespoke targeting strategies or invasive surgeries. Conversely, adeno-associated viruses (AAVs) can target specific tissues following intravenous injections. Here we show that cell-targeting properties of AAVs could be broadly conferred to nanomaterials. We develop a strategy to couple AAV capsids to nanoparticles that is invariant of viral serotype or nanomaterial chemistry and permits control over stoichiometry of the AAV-nanoparticle chimeras. The chimeras selectively escort nanoparticles into cell classes governed by AAV serotypes. When applied to magnetic nanoparticles, the AAV-nanoparticle chimeras enable magnetically localized gene delivery. In vivo, we show that leveraging the brain-targeting AAV serotype CAP-B10 achieves nanoparticle delivery to the parenchyma with [~]10% efficiency (% injected dose/g[brain]) while avoiding accumulation in the liver. The enhanced delivery efficiency and tissue specificity highlight the potential of AAV-chimeras as a versatile strategy to escort broad classes of nanotherapeutics to the brain and beyond.

bioengineering↗

bioRxiv2023

Magnetoelectric Nanodiscs Enable Wireless Transgene-Free Neuromodulation

Deep-brain stimulation (DBS) with implanted electrodes revolutionized treatment of movement disorders and empowered neuroscience studies. Identifying less invasive alternatives to DBS may further extend its clinical and research applications. Nanomaterial-mediated transduction of magnetic fields into electric potentials offers an alternative to invasive DBS. Here, we synthesize magnetoelectric nanodiscs (MENDs) with a core-double shell Fe3O4-CoFe2O4-BaTiO3 architecture with efficient magnetoelectric coupling. We find robust responses to magnetic field stimulation in neurons decorated with MENDs at a density of 1 {micro}g/mm2 despite individual-particle potentials below the neuronal excitation threshold. We propose a model for repetitive subthreshold depolarization, which combined with cable theory, corroborates our findings in vitro and informs magnetoelectric stimulation in vivo. MENDs injected into the ventral tegmental area of genetically intact mice at concentrations of 1 mg/mL enable remote control of reward behavior, setting the stage for mechanistic optimization of magnetoelectric neuromodulation and inspiring its future applications in fundamental and translational neuroscience.

bioengineering↗

bioRxiv2023

The unexpected consequences of predictor error in ecological model selection

1O_LIThe ability to select statistical models based on how well they fit an empirical dataset is a central tenet of modern bioscience. How well this works, though, depends on how goodness-of-fit is measured. Likelihood and its derivatives (e.g. AIC) are popular and powerful tools when measuring goodness-of-fit, though inherently make assumptions about the data. One such assumption is absence of error on the x-axis (i.e. no error in the predictor). This, however, is often not correct and deviations from this assumption are often hard (or impossible) to measure. C_LIO_LIHere, we show that, when predictor error is present, goodness-of-fit as perceived using likelihood will increase with decreases in sample size, effect size, predictor error and predictor variance. This results in predictors with increased effect size, predictor variance or predictor error being punished. As a consequence, we suggest that larger effect sizes are biased against in likelihood-based model comparison. Of note: (i) this problem is exacerbated in datasets with larger samples sizes and a broader range of predictor values - typically considered desirable biological data collection; and (ii) the magnitude of this effect is non-trivial given that proxy error (caused by using correlates of a predictor rather than the predictor itself) can lead to unexpectedly high amounts of error. C_LIO_LIWe investigate the effects of our findings in an empirical dataset of wood anemone (Anemone nemorosa) first flowering date regressed against temperature. Our results show that the proxy error caused by using air temperature rather than ground temperature results in a {triangleup}AIC of around 3. We also demonstrate potential consequences for model selection procedures with autocorrelation (e.g. sliding window approaches). Via simulation we show that in the presence of predictor error AIC will favour autocorrelated, lower effect size predictors (such as those found on the edges of predictive windows), rather than the a priori specified true window. C_LIO_LIOur results suggest significant and far-reaching implications for biological inference with model selection for much of todays ecology using observational data under non-experimental conditions. We assert that no obvious, globally-applicable solution to this problem exists; and propose that quantifying predictor error is key in accurate ecological model selection going forward. C_LI

ecology↗

bioRxiv2022

Reprogramming brain immunosurveillance with engineered cytokines

Immune surveillance of the brain is regulated by resident non-neuronal cells and the blood-brain barrier.1 Dys-regulation of immunosurveillance is a hallmark feature of several diseases2-5 including brain tumors6 that interact with and rely heavily on immune cells,7 suggesting that disrupting the neuroimmunology of tumors could slow their progression. Yet few tools are available to control brain immunology in vivo with local precision, and fewer yet are used for therapeutic intervention. 2 Here, we propose engineered cytokines as a neuroimmune-modulation platform. We demonstrate that the residence time of cytokines in the brain can be tuned by binding them to the extracellular matrix or synthetic scaffolds. We then show that the aluminum hydroxide adjuvant (alum) is retained in the brain >2 weeks. Tethering of inflammatory cytokines such as interleukins (IL) 2 and 12 to alum yields extended neuroinflammation and brain immunosurveillance after intracranial administration, while avoiding systemic toxicity. In mouse models of both immunologically hot and cold brain tumors, the intracranial deposition of alum-tethered cytokines causes significant delay in tumor progression. RNA profiling reveals that engineered cytokines engage both innate and adaptive immunity in the brain. These findings suggest that engineered cytokines can reprogram brain immunosurveillance, informing the development of future therapies for neuroimmune diseases.

bioengineering↗