BOSTON – Oxygen is vital to life, and doctors can provide supplemental oxygen to patients through face masks and nasal tubes, but there are no methods available to deliver oxygen directly to cells.
This capability would initially be useful as a research tool, but could eventually have important medical applications, for example, to improve therapies that lose effectiveness when oxygen levels are low.
As reported in PNAS, researchers at Massachusetts General Hospital (MGH) recently developed a technology that allows them to engineer cells to produce oxygen on demand in response to an added chemical.
The work was led by Vamsi K. Mootha, MD, Professor of Systems Biology and Medicine in MGH’s Department of Molecular Biology, whose lab focuses on mitochondria. These specialized compartments within cells produce energy and need oxygen to do so. “We are interested in how mitochondria, cells and organisms adapt to changes in environmental oxygen,” says Mootha.
Currently, if scientists want to manipulate the oxygen levels of cells in the laboratory, they place a petri dish containing cells in an environmentally controlled chamber. While this is helpful, they cannot change the oxygen levels in selected cells at a specific time.
“Out of this need arose the idea of a genetically encoded system that could be deployed in human cells to produce their own oxygen on demand,” says Mootha.
The technology involves simultaneously expressing a bacterial transporter and enzyme within 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 new genetic technology SNORCL, for supplemental oxygen released from ChLorite. The first-generation SNORCL is capable of producing short, modest pulses of oxygen within the cells in response to added chlorite.
“In the short term, SNORCL is really for the research field, to evaluate the role of oxygen in signaling, metabolism and physiology in great detail. But in the future, SNORCL-based technologies could have a variety of clinical uses,” says Mootha.
For example, tumors often have low oxygen levels that limit the effectiveness of some cancer therapies. SNORCL could be used to improve the efficacy of these therapies in these settings.
Other co-authors include Andrew L. Markhard, Jason G. McCoy, and Tsz-Leung To.
This work was supported by the Howard Hughes Medical Institute.
Document cited:
Markhard, AL, McCoy, JG, To, TL, & Mootha, VK (2022). A genetically encoded system for the generation of oxygen in living cells. Proceedings of the National Academy of Sciences of the United States of America, 119(43), e2207955119. https://doi.org/10.1073/pnas.2207955119
About Massachusetts General Hospital
Massachusetts General Hospital, founded in 1811, is Harvard Medical School’s original and largest teaching hospital. The Mass General Research Institute conducts the nation’s largest hospital research program, with annual research operations of more than $1 billion and includes more than 9,500 researchers working in more than 30 institutes, centers and departments. In July 2022, Mass General was named #8 on the US News & World Report list of “America’s Best Hospitals.” MGH is a founding member of the Mass General Brigham Health System.
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