Oxygen is important for all times, and clinicians can provide supplemental oxygen to patients through face masks and nasal tubes, but there are not any methods available for delivering oxygen directly into cells.
This capability could be useful initially as a research tool but could eventually have necessary medical applications-;for instance, to boost therapies that lose effectiveness when oxygen levels are low.
As reported in PNAS, investigators at Massachusetts General Hospital (MGH) recently developed a technology that permits them to engineer cells to make oxygen on demand in response to an added chemical.
The work was led by Vamsi K. Mootha, MD, a Professor of Systems Biology and Medicine within the Department of Molecular Biology at MGH, whose laboratory focuses on mitochondria. These specialized compartments inside cells produce energy, and so they require oxygen to accomplish that. “We’re keen on how mitochondria, cells, and organisms adapt to changes in ambient oxygen,” says Mootha.
Currently, if the scientists want to control cells’ oxygen levels within the lab, they place a petri dish containing cells in an environmentally controlled chamber. While this is helpful, they can not change oxygen levels in select cells at a particular time.
“From this need got here the thought for a genetically encoded system that might be deployed in human cells to provide their very own oxygen on demand,” says Mootha.
The technology involves concurrently expressing a transporter and a bacterial enzyme inside a cell-;together, these proteins promote the uptake of chlorite into the cell and enzymatically convert it into oxygen and chloride.
The researchers call their latest genetic technology SNORCL, for SupplemeNtal Oxygen Released from ChLorite. The primary generation SNORCL is capable of manufacturing short and modest pulses of oxygen inside cells in response to added chlorite.
Within the near-term SNORCL is absolutely for the research arena, for evaluating the role of oxygen in signaling, metabolism, and physiology in great detail. But then in the longer term, technologies based on SNORCL could have quite a lot of clinical uses.”
Vamsi K. Mootha, MD, Professor of Systems Biology and Medicine, Department of Molecular Biology, MGH
For instance, tumors often have low oxygen levels that limit the effectiveness of some anti-cancer therapies. SNORCL is likely to be used to enhance these therapies’ effectiveness in such environments.
Additional co-authors include Andrew L. Markhard, Jason G. McCoy, and Tsz-Leung To.
This work was supported by the Howard Hughes Medical Institute.
Source:
Massachusetts General Hospital
Journal reference:
Markhard, A. L., McCoy, J. G., To, T. L., & Mootha, V. K. (2022). A genetically encoded system for oxygen generation in living cells. Proceedings of the National Academy of Sciences of the US of America, 119(43), e2207955119. https://doi.org/10.1073/pnas.2207955119