What if we could edit our DNA? Cut out the parts that we didn’t want and stitch what was left back together? Over the last three years, science has begun moving rapidly closer to making this possibility a reality with new technology called CRISPR-Cas9.
Last month, two molecular biologists/geneticists were honored as L’Oreal UNESCO Laureates in a ceremony in Paris, France. The highly competitive, international award recognizes outstanding contributions to the advancement of science from five laureates each year. The 2016 Laureates include Dr. Jennifer Doudna of the US and Dr. Emmanuelle Charpentier of France and Germany who are both leading the development of technologies related to CRISPR-CAS9. Both women were also recently awarded the Breakthrough Prize, an honor that comes with a whopping $3 million.
What Is CRISPR-Cas9?
Humans are incredibly adaptable, enabling our survival in even the most remote corners of our planet. Over generations and generations of time, those with the genetics best honed for survival do so, and our DNA adapts making us more fit as a species.
But what if we could skip all of that evolution? Knowing that eventually humans could develop some kind of immunity is likely of little comfort if you have a loved one suffering from a life-threatening illness. What if, instead, we could find an evolutionary short cut and edit our DNA directly?
CRISPR-Cas9 has the potential to prevent sickle cell disease, a blood disorder that affects millions of people from early childhood, and has already been shown to eliminate Hepatitis C and HIV genomes in human cells. How does it accomplish all of that? Through a type of gene editing that bacteria already use in their own immune systems.
CRISPR stands for “clustered regularly interspaced short palindromic repeats,” a pattern noticed in 1987 by Japanese scientists to exist in the DNA of E. Coli bacteria. In other words, the bacterial DNA was packaged in repeating sequences separated by short, non-repeating spacers of other DNA sequences. This pattern was recognized in other types of bacteria and single-celled organisms.
After extensive research, scientists soon realized the power behind this simple pattern. The spacers of seemingly random DNA sequences were actually copies of the DNA from harmful viruses that the bacteria had encountered. By keeping what is akin to a diary of information on its enemies, the bacteria can use that DNA information to prevent future exposures to those viruses from escalating.
Each CRISPR region in the bacterial DNA also contains an RNA molecule and CRISPR-associated proteins (called Cas proteins). The bacteria can make a copy of the viral DNA contained in a spacer sequence and transfer it to the RNA molecule, which acts as transport. The Cas proteins then move together with the viral-encoded RNA molecule through the cell on a hunt for a matching virus. When they find one, the RNA can latch onto it while the Cas proteins splice it, preventing the virus from replicating further. Thus, CRISPR is effectively the bacteria’s immune system.
The most well-understood of the Cas proteins is Cas9, which resides in streptococcus pyogenes which is, you guessed it, the bacteria that causes strep throat. Cas9 has an advantage over some other proteins in that it can identify longer strings of bases in a DNA sequence. Thus, Cas9 can target a specific gene with less risk of identifying a smaller subset of the DNA pattern somewhere else and is thus less likely to cut in the wrong spot.
In 2012, Doudna and Charpentier published a revolutionary paper in Science titled "A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity." For those of us who aren’t biochemists, their paper announced that they had been able to use this bacterial CRISPR-Cas9 system, in concert with a programmable RNA molecule, as a new gene-editing tool to find, slice, and replace any gene sequence.