Biology subjects

Beschorner, N.

Publications and source records attributed to Beschorner, N..

3 recordsLinked to original sources

bioRxiv2026

Scaling of anesthesia-dependent cerebrospinal fluid dynamics across rat and pig brains

This study presents a novel in vivo neuroimaging approach using dynamic single photon emission computed tomography (SPECT/CT) to investigate cerebrospinal fluid (CSF) dynamics in pigs, a translationally relevant model due to their human-like brain structure. The distribution, brain penetration of [99mTc]-DTPA and subsequent clearance were followed by brain SPECT for three hours after injection into the cisterna magna of anesthetized pigs and rats. To investigate the effects of anesthesia and across-species effects, we examine CSF dynamics under two types of anesthesia, propofol and ketamine/dexmedetomidine (K/D), and compare the outcome in pigs to that of rats, in which we also compared isoflurane. Propofol and K/D produced largely similar tracer distribution patterns across both pigs and rats: In both species, K/D was associated with higher tracer penetration into the dorsal striatum compared to propofol while neither species showed a tracer accumulation difference in the thalamus. K/D also increased intracranial radiotracer retention and reduced urinary tracer clearance in rats, but not in pigs. In rats, propofol and isoflurane showed similar tracer distribution, reflecting their shared GABAergic mechanism of action. The differences observed between pigs and rats may reflect species-specific physiology, differences in anesthesia dosing, or methodological factors. The work demonstrates the feasibility of using SPECT/CT to study CSF transport in the large gyrencephalic pig brain to advance understanding of human brain fluid dynamics.

neuroscience↗

bioRxiv2026

Development of a recombinant adeno-associated virus vector for human T lymphocyte- and natural killer cell-targeted gene therapy

Recombinant adeno-associated virus (rAAV) vectors are widely used for gene delivery but show limited efficiency in immune cells, including T lymphocytes and natural killer (NK) cells. To overcome this barrier, we developed a modular rAAV vector engineering strategy that integrates capsid retargeting with genome optimization. We report a CD7-targeted rAAV vector (CD7-AAV6/9) featuring a nanobody-fused hybrid capsid derived from a rationally selected chimeric combination of AAV6 and AAV9. CD7-AAV6/9 enables efficient and selective transduction of immortalized and primary human T and NK cells in vitro and in vivo in a humanized mouse model, achieves high production titers, and exhibits markedly reduced off-target transduction compared with wild-type serotypes. In parallel, we demonstrate that incorporation of a human gene-derived intron into the vector genome overcomes host-mediated transcriptional repression and enables robust transgene expression in human CD7 T lymphocyte and NK cell populations. To our knowledge, this represents the first application of intron-mediated enhancement in a rAAV vector context. Together, our findings establish an integrated capsid-genome design framework for targeting human T and NK cells, notoriously challenging immune cell populations for gene therapy, and provide a versatile platform readily adaptable to alternative surface markers and therapeutic payloads.

molecular biology↗

bioRxiv2022

An in vivo pig model for testing novel PET radioligands targeting cerebral protein aggregates

Positron emission tomography (PET) has become an essential clinical tool for diagnosing neurodegenerative diseases with abnormal accumulation of proteins like amyloid-{beta} or tau. Despite many attempts, it has not been possible to develop an appropriate radioligand for imaging aggregated -synuclein in the brain for diagnosing, e.g., Parkinsons Disease. Access to a large animal model with -synuclein pathology would critically enable a more translationally appropriate evaluation of novel radioligands. We here establish a pig model with cerebral injections of -synuclein preformed fibrils or brain homogenate from postmortem human brain tissue from individuals with Alzheimers disease (AD) or dementia with Lewy body (DLB) into the pigs brain, using minimally invasive surgery and validated against saline injections. In the absence of a suitable -synuclein radioligand, we validated the model with the unselective amyloid-{beta} tracer [11C]PIB, which has a high affinity for {beta}-sheet structures in aggregates. Gadolinium-enhanced MRI confirmed that the blood-brain barrier was intact. A few hours post-injection, pigs were PET scanned with [11C]PIB. Quantification was done with Logan invasive graphical analysis and simplified reference tissue model 2 using the occipital cortex as a reference region. After the scan, we retrieved the brains to confirm successful injection using autoradiography and immunohistochemistry. We found four times higher [11C]PIB uptake in AD-homogenate-injected regions and two times higher uptake in regions injected with -synuclein-preformed-fibrils compared to saline. The [11C]PIB uptake was the same in non-injected (occipital cortex, cerebellum) and injected (DLB-homogenate, saline) regions. With its large brains and ability to undergo repeated PET scans as well as neurosurgical procedures, the pig provides a robust, cost-effective, and good translational model for assessment of novel radioligands including, but not limited to, proteinopathies.

neuroscience↗