MODIFIED FROM ISTOCK.COM/THORBJORN66One of the biggest surprises to come from sequencing efforts of the past 15 years is how little of the human genome is translated into proteins. We have about as many protein-coding genes, 20,000, as the roundworm Caenorhabditis elegans. And yet, roughly 80 percent of our genome is transcribed into RNA. Long or short, looping or straight, rigid or not, most of this rabble of transcripts never crosses what was once thought of as molecular biology’s finish line by being translated into proteins. Those RNAs may well harbor some explanations for why we differ from worms, and they often turn up in genome-wide studies as being associated with disease. But most of these so-called noncoding RNAs have no known function.
That’s where CRISPR/Cas9 serves an important role. Soon after scientists developed the system as a gene-editing method, they went to work on versions they could use to dial gene expression up or down, not by cutting genes and inserting new genetic material, but by having Cas9 take up residence on predetermined sites on the genome to initiate or stop transcription. These innovations, known as CRISPR activation (CRISPRa) and CRISPR inhibition (CRISPRi), are allowing users to tweak the expression not only of protein-coding genes but also of genes for noncoding RNAs to probe the functions of those transcripts.
Although more researchers are beginning to use CRISPRa and CRISPRi, the methods are—like anything CRISPR—still new. “When it comes to these technologies, we are all beta testers,” says ...
