Since its discovery, researchers have hailed Cas9—a protein “machine” that can be programmed by a strand of RNA to target specific DNA sequences and to precisely cut, paste, and turn on or turn off genes—as a potential key to unlocking a host of new treatments and therapies for genetic conditions, but only if they fully understand how it works.
That’s where David R. Liu and his students Vikram Pattanayak and John Guilinger come in.
Liu, a Harvard professor of chemistry and chemical biology and an investigator with the Howard Hughes Medical Institute, joined with Professor Jennifer Doudna of the University of California, Berkeley, to lead an effort to develop a detailed “specificity profile” for Cas9—data to reveal how accurately Cas9 can home in on the DNA sequence it is programmed to target, and how susceptible the protein/RNA complex is to acting on decoy off-target sequences instead. The work was described in a paper published last month in Nature Biotechnology.
“A major issue that will determine the extent to which technologies like Cas9 are useful research tools, especially for human therapeutics, is how specific they are,” Liu said.
“It’s widely understood that the ability to manipulate the structure of our genomes has the potential to have a profound impact on human health,” he added. “But before you give a patient some treatment that will change their genes, you need to be very confident that it’s not going to have unintended effects elsewhere, because the difference between cutting an on-target site and an off-target site could mean treating a disease or triggering the development of cancer.”
Read more at: Phys.org