 Since the discovery of DNA's fundamental role in building and sustaining life, scientists have dreamed of having the ability to easily edit DNA in very precise ways. But why would they want to do this? Well, making specific changes to DNA sequences can help scientists better understand the function of certain genes, produce specific disease models, or even repair defective genes that cause diseases in humans. This is an exciting prospect, but methods to try and do this weren't practical or widely applicable. However, a few years ago, a gift from biology came from the basic research of the bacteria immune system, which gave scientists the ability to easily, customisably, and precisely edit genomes. Bacteria evolved in genius ways of protecting themselves against pathogens such as viruses by using a system called CRISPR-Cas. CRISPR's are stretches of DNA sequence found in the bacterial genome. In close proximity to CRISPR are the cas genes, which encode proteins necessary for the CRISPR system. Up until a few years ago, what was known about the CRISPR-Cas system is that bacteria infected by a virus incorporate elements of the virus's DNA into the CRISPR sequence. This protected the bacteria from future infection by this virus. Scientists observed that when a virus invades a bacterium, the CRISPR DNA produces one or two small RNAs called CR RNA and Tracer RNA. These RNAs bound to cas proteins and formed complexes that cut the DNA of the invading virus, thus protecting the bacteria from infection. But many questions still remained, how did the small RNAs and cas work together to detect and destroy viral DNA? In 2012, a group of scientists made a major breakthrough and discovered not only how the CRISPR RNAs and cas cut DNA, but also how to create a new technique to specifically change the DNA sequence of any organism with great ease. This discovery came from a group of scientists led by Jennifer Dunna at UC Berkeley and Emmanuel Charpentier at UMEA University in Sweden. They published their results in science in an article titled, A Programmable Dual RNA Guided DNA and a Nuclease in Adaptive Bacterial Immunity. So what exactly did these scientists find and why is it so important for future biomedical research? First, the scientists dissected how Cas9 and the two RNAs can cut DNA. They found that the two RNAs, CR RNA here in red and Tracer RNA here in green, pair up, recruit Cas9 protein and direct it to bind the target DNA via the complementary base pairing between the red CRISPR RNA and the target DNA. Once at the proper DNA site, Cas9 cleaves both DNA strands. This cleavage occurs at a very specific and conserved position that is dictated by the sequence in the red CRISPR RNA molecule. This process is similar to finding your plane by matching the gate number to the one on your boarding pass. The scientists then wondered if they could engineer one RNA molecule that mimicked the structure of the CRISPR RNA and Tracer RNAs bound together that would guide Cas9 to cut DNA at a specific location. The scientists designed one RNA molecule that consisted of the red and green RNA molecules connected together by a hairpin structure. In this case, they engineered the RNAs to target specific sequences of the gene encoding the green fluorescent protein, GFP. They added the engineered RNA molecules to the GFP DNA sequence along with the Cas9 protein and asked whether Cas9 would cut GFP DNA at specific sequences. And it did. When the RNA molecules were designed to bind to different regions of the GFP sequence, the GFP DNA sequence was cleaved at that specific location. On a gel that separates DNA according to size, you can see distinctly sized fragments of the GFP DNA molecule resulting from having been cut in a specific location. This was huge as it meant that scientists could engineer one RNA sequence, introduce Cas9, and cut DNA at a specific location of their choice. By having this simple and easily programmable system, scientists can now induce breaks in the DNA at precise locations. When the cell tries to repair the broken DNA strands by ligating them back together, it often causes a small insertion or deletion that changes the DNA sequence. Scientists can take advantage of this process to add or remove specific DNA sequences at the site of the break. We now have a DNA word processor that can be used to change genome sequences, including our own. CRISPR has a bright future ahead to advance our understanding of human disease by creating a tool from basic research that is now widely used in the fields of molecular biology and genetics to change the genomes of any organism. But much work needs to be done to make the system more reliable. Use of the CRISPR system to edit human embryos is also a controversial issue and researchers have already started the conversation about using this technology ethically and safely to advance human knowledge. This video has been provided to you by Eureka Science and iBiology, bringing the world's best biology to you.