Engineering water exchange is a safe and effective method for magnetic resonance imaging in diverse cell types
Year: 2024
Type: article
Abstract: Aquaporin-1 (Aqp1), a water channel, has garnered significant interest for cell-based medicine and in vivo synthetic biology due to its ability to be genetically encoded to produce magnetic resonance signals by increasing the rate of water diffusion in cells. However, concerns regarding the effects of Aqp1 overexpression and increased membrane diffusivity on cell physiology have limited its widespread use as a deep-tissue reporter. In this study, we present evidence that Aqp1 generates strong diffusion-based magnetic resonance signals without adversely affecting cell viability or morphology in diverse cell lines derived from mice and humans. Our findings indicate that Aqp1 overexpression does not induce ER stress, which is frequently associated with heterologous expression of membrane proteins. Furthermore, we observed that Aqp1 expression had no detrimental effects on native biological activities, such as phagocytosis, immune response, insulin secretion, and tumor cell migration in the analyzed cell lines. These findings should serve to alleviate any lingering safety concerns regarding the utilization of Aqp1 as a genetic reporter and should foster its broader application as a noninvasive reporter for in vivo studies.
Institution: University of California, Santa Barbara
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,790
Funders: National Science Foundation, Brain and Behavior Research Foundation, Searle Scholars Program, Cancer Research Coordinating Committee, National Institutes of Health, University of California, Santa Barbara, National Institute on Drug Abuse, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, Army Research Office, Institute for Collaborative Biotechnologies
Awards: G321649331, A genetically encoded MRI reporter for noninvasive imaging of activity-dependent gene expression in neurons, G5008113308, Materials Research Science and Engineering Center at UCSB, Investigating the role of AAA+-ATPases in peroxisome biology, Engineering fluorescence and magnetic resonance reporter genes for imaging biological function in hypoxic cells and in vivo, Metal-free, genetically encoded reporters for calcium recording with MRI, Signal Integration during Phagocytosis, Defining DNA resection and protein localization changes that occur during DSB repair
OpenAlex ID: W4394996258