Since its discovery in 2011, CRISPR/Cas9 is at the center of one of today’s most-discussed science discoveries: a technology that allows human genome editing by adding or removing genetic material at will. This technology represents a versatile and profoundly transforming research tool, incredibly useful for many inherited genetic diseases or cancers as well as, potentially, opening the road to “engineered humans”.

CRISPR/Cas9 is a mechanism present in many prokaryotes that protects them from invasion by foreign DNA (viruses). This mechanism allows to recognize specific DNA sequences and then use the Cas9 enzyme, which is like a molecular pair of scissors, to chop that DNA sequence which, in the case of bacteria, will kill the virus. What Doudna and Charpentier have been able to do is to hijack that system for eukaryotic cells so that just by guiding the Cas9 enzyme with an engineered RNA molecule to any specific DNA segment, they get the Cas9 enzyme to cut that sequence in a precise and directed manner. Recent advances in the CRISPR/ Cas9 system have dramatically facilitated genome engineering in various cell systems, increasing efficiency and reducing “off-target effect” (DNA being cut at some non-desired sites).

We asked some of the NCCR Chemical Biology researchers to explain how they apply the CRISPR/Cas9 to their research, describe how this technology speeds up discoveries in their field while comment on the robustness of the technique and finally estimate the impact of this paradigm shift.

The interviews that follow highlight the spectrum of applications of this technology:

• Towards a better understanding of lipid homeostasis
• CRISPR/Cas9 for gene editing in zebrafish
• Insights into ciliary signaling using a CRISPR-based screen

 

Main picture: CRISPR-associated protein Cas9 (white) from Staphylococcus aureus based on PDB ID 5AXW. Copyright: Thomas Splettstoesser (www.scistyle.com)