Researchers at Stanford University have developed a new CRISPR tool that can not only switch genes on and off but can also sense the cellular environment and determine when certain genes need to be activated or deactivated.
In healthy cells, cellular processes are carefully controlled through thousands of circuits that monitor conditions and respond to different biological signals. When disease strikes, such as cancer, those cellular processes cease to function as they should. In the case of cancer, genes go awry and can be switched on when they should be off and off when they should be on. The abnormal behavior of one gene can also affect the behavior of another. With cancer and other complex diseases, several genes are often malfunctioning at the same time.
Stanley Qi, Ph.D. Assistant Professor and the Department of Bioengineering and Department of Chemical and Systems Biology at the Stanford ChEM-H Institute and his team had previously developed a CRISPR-Cas12 gene editing tool that could perform multiple actions inside cells, such as switching multiple genes on and off simultaneously. The latest research takes that concept a step further and adds monitoring capabilities to create a sense and respond system.
Qi worked with graduate student Hannah Kempton to modify their CRISPR tool to have the Cas12 protein component activated in response to multiple faulty biological signals. The Cas12 gene editing component of the tool would then activate or deactivate genes based on the defects that caused the malfunctioning. The CRISPR tool monitors several different genetic circuits at once and can detect abnormalities and will kick into action at the right time.
“Although the CRISPR-Cas system has been harnessed for synthetic manipulation of the genome, it has not been fully utilized for complex environmental signal sensing, integration, and actuation,” wrote the researchers. “Here, we develop a split dCas12a platform and show that it allows for the construction of multi-input, multi-output logic circuits in mammalian cells.”
The ability to sense multiple signals at once means it is possible to identify a disease state with greater precision and administer therapy more safely.
Qi’s lab has applied for a provisional patent for their new CRISPR tool, which has possible uses beyond the treatment of diseases such as cancer. The researchers believe their CRISPR tool could be used to help the body recover from injury by activating genetic circuits to trigger stem cells to differentiate into new heart, bone, or liver cells to replace cells that cannot be repaired.
You can read more about the study in the paper – Multiple Input Sensing and Signal Integration Using a Split Cas12a System – which was recently published in the journal Molecular Cell. DOI: 10.1016/j.molcel.2020.01.016