Biology subjects

Gelabert, A.

Publications and source records attributed to Gelabert, A..

2 recordsLinked to original sources

bioRxiv2026

Minimally Invasive in Situ Perfusion Method for Targeted AAV Delivery in Native Kidney: Proof of Concept in Pigs

Currently, there is not any method for efficient and targeted delivery of gene therapies using viral vectors to the native kidneys. Adeno-associated viruses (AAV) are limited by hepatotoxicity and poor kidney tropism. This study aimed to develop a minimally invasive approach that overcomes both challenges. We evaluated in pigs a technique leveraging external perfusion systems to transiently isolate native kidney vascularization. Using a percutaneous femoral approach, fluoroscopy-guided catheterization of the kidney artery and vein enabled the establishment of a temporary isolated kidney perfusion circuit permitting native kidney in-situ perfusion. AAV delivery was then assessed by detecting construct encoding Td-Tomato protein, its mRNA and fluorescence 6 days after the perfusion. The method was achieved with two different external perfusion systems and was not associated with procedure related mortality or any major complication. Td-Tomato was detected in the perfused kidney without a significant detection in the liver which showed no inflammatory infiltrates. We developed, in pigs, a minimally invasive method permitting in-situ native kidney perfusion that enables kidney-targeted AAV delivery. Besides, it limits liver off-target transduction, potentially reducing its main side effect, hepatotoxicity, when AAV is systemically injected. It offers fast-track translational possibilities for developing kidney-targeted gene therapies. Finally, it may permit additional non-AAV therapeutics for patients with kidney diseases.

genetics↗

bioRxiv2019

Single-cell determination of iron content in magnetotactic bacteria: implications for the iron biogeochemical cycle

Magnetotactic bacteria (MTB) are ubiquitous aquatic microorganisms that biomineralize dissolved iron from the environment into intracellular nanoparticles of magnetite [Fe(II)Fe(III)2O4] or greigite [Fe(II)Fe(III)2S4] in a genetically controlled manner. After cell death, these magnetite and greigite crystals are trapped into sediments which effectively removes iron from the soluble pool. MTB may significantly impact the iron biogeochemical cycle, especially in the ocean where dissolved iron limits nitrogen fixation and primary productivity. Although MTB are ubiquitous in the environment, their impact on the biogeochemical cycling of metallic elements is still poorly constrained. A thorough assessment of the mass of iron incorporated by MTB has been hampered by a lack of methodology to accurately measure the amount of, and variability in, their intracellular iron content. Here, we quantify the mass of iron contained in single MTB cells of the model organism, Magnetospirillum magneticum sp. AMB-1, using a time-resolved mass spectrometry methodology. Bacterial iron content depends on the external iron concentration, and reaches a maximum value of 10-6 ng of iron per cell when bacteria are cultivated with initial iron concentrations of 100 M or higher. From our experimental results, we calculated the flux of dissolved iron incorporation into natural MTB populations and conclude that MTB may mineralize a significant fraction of environmental dissolved iron into crystals.

microbiology↗