CRISPR: a new era in gene editing
If you’ve been paying attention to science news, you’ve probably heard a lot about genome editing and the technology that’s made it so widely used, CRISPR (pronounced “crisper”). Most controversially, a team in China edited the genomes of human embryos — a landmark event that raised concerns of a slippery slope towards unethical uses. Nonetheless, few doubt that the technology will revolutionize research and treatment of genetic disease.
What is it? CRISPR stands for clustered regularly interspaced short palindromic repeats. But in a nutshell, it’s a way of editing the genome in a specific, directed change in DNA — changing one or more nucleotides (the letters of the genetic code), inserting more, or deleting them.
How does it work? Editing genes using the CRISPR system requires (1) a guide RNA that specifies the location of the change, (2) Cas9, the enzyme that cuts both strands of DNA, and, if the goal is to replace or insert nucleotides, (3) a plasmid (circular piece of DNA) containing nucleotides to be inserted between the newly freed ends. These three tools are used to make very specific changes to specific genes.
Why is it exciting for research?
- Disease models — CRISPR makes genetic modification of animals incredibly easy, which is important for understanding how individual genetic changes contribute to disease. Whereas making a knockout mouse (in which a certain gene is inactivated) used to take a year or two, it’s now possible in a few weeks.
CRISPR also makes it possible to manipulate genes in a much wider variety of species than with old technologies — so far, over three dozen. This flexibility is a huge advantage because mice aren’t always the best models for human diseases. For example, ferrets are ideal for studying influenza because they sneeze, and rabbits are often preferred for ophthalmological research because their eyes are larger and more similar to human eyes than those of rodents.
- Determining gene function — CRISPR has been widely used to examine whether specific genes are involved in a given cellular process. CRISPR-based functional screens consist of eliminating each gene in different cells, and then measuring the effect. Compared to older techniques, it gives a clearer result because it more thoroughly prevents gene expression and is less likely to affect other genes.
What’s the potential for therapy? Before CRISPR can be used to treat disease, it must first be refined to minimize the chances of unintentionally changing other genes, and that may take years. Still, many experts believe it will eventually be used in the clinic.
- Correcting disease-causing mutations in patients — Gene editing technology revitalizes the promise of gene therapy, which failed in the past because older methods could disrupt genes in ways that lead to cancer. CRISPR therapy will be simpler for diseases of the retina, liver, or muscle because tools are currently available to get CRISPR components into those cells. Another tissue to which gene editing could be fairly readily applied is bone marrow, where cells could be removed for gene editing in a lab, then returned to the patient.
- Preventing developmental disorders by gene editing in embryos — This application faces not only the technical challenges of developing reliable genetic tests and a safe means of delivering the CRISPR components to an embryo, but also obvious ethical concerns. Future FDA approval of embryonic gene editing would require public acceptance and agreement on when such an extreme intervention is warranted.